Novel marker for the diagnosis and therapy of tumours

ABSTRACT

The present invention relates to novel markers for tumors, preferably CTCL. The present invention also relates to the use thereof for the diagnosis and/or therapy of tumoral diseases, preferably CTCL.

[0001] The present invention relates to the use of novel markers for thediagnosis and/or therapy of tumoral diseases, preferably CTCL.

[0002] Cutaneous T-cell lymphomas (CTCL) represent a heterogenous groupof diseases in which CD4 T-cells prevail as the malignant cell type. Inmost cases, the monoclonal or at least oligoclonal origin of themalignant cells is documented by means of T-cell receptorrearrangements. Along with various other subtypes, mycosis fungoides andthe Sézary syndrome (SS) represent the most frequent forms of CTCL. Bothdiseases are monoclonal T-helper memory lymphomas which arecharacterized by cutaneous plaques, tumors or erythrodermia, SS beingadditionally characterized by a generalized lymphadenopathy and thepresence of neoplastic T-cells in the peripheral blood.

[0003] The therapeutic approaches comprise the stage-dependent selectionof PUVA (psoralen and UV-A), retinoids, interferon α-2a in combinationwith acitretin or PUVA, various immunomodulators, electron irradiationor extracorporeal photopheresis. These methods are successful in theearly disease stages but not in the aggressive subsequent stages.Immunological therapies, e.g. vaccination with peptides orpeptide-loaded dendritic cells as used already for treating melanomas,are counted among the possibly useful future therapies for CTCL.

[0004] The presence and activity of CD8⁺ cells in the case of CTCL wascorrelated with the prognosis. It was possible to show thatCD8⁺-reactive infiltrates are CTCL-specific and lytic. Thus, althoughimmunotherapies might represent a promising conception for treatingCTCL, a precondition for such a strategy is the identification oftumor-specific antigens. In this connection, the T-cell receptor as suchwas proposed as an antigen (similar to the idiotype-immunoglobulins as atarget for B-cell-specific T-cells). However, in both cases there is thedrawback that the antigen T-cell receptor of each individual patientshould be identified. In summary, it should, however, be pointed outthat no tumor-associated antigens are currently known for tumor kinds,such as CTCL, and therefore the chances of a specific diagnosis and/ortherapy are greatly limited.

[0005] The present invention is thus substantially based on thetechnical problem of identifying and providing markers (genes and/ortheir products) which are correlated with tumors, in particular CTCL,and are optionally of diagnostic use and/or, based on a vaccinationtherapy, of therapeutic use.

[0006] The solution to this technical problem was achieved by providingthe embodiments characterized in the claims.

[0007] Surprisingly, a number of genes were found the expression ofwhich is correlated with CTCL. In the experiments resulting in thepresent invention, CTCL-specific antigens were identified by screening atestis cDNA library and/or a cDNA library established from tumor RNA ofdifferent cutaneous lymphomas, with serums from tumor patients. About3×10⁶ recombinants were screened with serums from patients sufferingfrom Sézary syndrome or Mycosis fungoides. The results show that tumorantigens from CTCL tumors can be identified using antibodies derivedfrom tumor patients. It was possible to identify positive clonesbelonging to 19 different genes/ORFs which also comprised five formerlyunknown sequences. All of the tumor antigens found are specific, i.e.only tumor patients but no healthy persons produce antibodies directedthereagainst although 13 of these tumor antigens are expressed in atleast 21 % of the tested control tissues. Moreover, a tumor-specificantigen was found which is only expressed in testis and tumor tissues.This antigen is se2-1, which was found in a CTCL tumor. This gene showssome similarity with SCP-1, a protein correlated with mitosis. Fourserums from CTCL patients reacted with different SCP-1-similar clones.Thus, it was possible by means of the experiments leading to the presentinvention to identify CTCL-associated antigens for the first time(irrespective of the T-cell receptor) which are thus valuable tumormarkers. The identification of such antigens is of interest since thecoded proteins and peptides derived therefrom serve as targetstructures, e.g. for cytotoxic cells, and can be used as antigens forthe production of diagnostic or therapeutic antibodies. For tumortherapy, the peptides encoded by the nucleic acids according to theinvention and/or fragments thereof can be applied either directly or beloaded onto antigen-presenting cells. The peptides representing antigenscan also be expressed in different cells (e.g. dendritic cells asantigen-presenting cells) by means of vectors. Furthermore, theidentified nucleic acids serve as a basis for developing diagnostictests to ensure a more reliable and early diagnosis in affected personsin future. Moreover, functional analyses of the proteins will no doubtcontribute to an understanding of tumor development. The nucleic acidsaccording to the invention should thus be regarded as candidate genesfor studying the pathomechanisms underlying different tumoral diseases,such as CTCL.

[0008] The subject matter of the present invention is thus a diagnosticcomposition containing at least one nucleic acid whose modifiedexpression is associated with a tumoral disease, the nucleic acidsequence comprising se2-5 (FIG. 1), se20-10 (FIG. 2), se57-1 (FIG. 3),se70-2 (FIG. 4), Lg1-2 (FIG. 5), se1-1 (FIG. 6), se2-1 (FIG. 7), se2-2(FIG. 8), se14-3 (FIG. 9), se20-4 (FIG. 10), se20-7 (FIG. 11), se20-9(FIG. 12), se33-1 (FIG. 13), se37-2 (FIG. 14), se89-1 (FIG. 15), L14-2(FIG. 16), L15-7 (FIG. 17), Li9-1 (FIG. 18), Li9-4 (FIG. 19), Lii5-2(FIG. 20), Lii10-6 (FIG. 21), Liii4-5 (FIG. 22) or GBP-TA (FIG. 23).

[0009] The subject matter of the present invention also relates to amedicament containing a nucleic acid sequence whose modified expressionis associated with a tumoral disease, the nucleic acid sequencecomprising se20-10 (FIG. 2), se57-1 (FIG. 3), Lg1-2 (FIG. 5), se1-1(FIG. 6), se2-1 (FIG. 7), se2-2 (FIG. 8), se14-3 (FIG. 9), se20-4 (FIG.10), se20-7 (FIG. 11), se20-9 (FIG. 12), se33-1 (FIG. 13), se37-2 (FIG.14), L14-2 (FIG. 16), L15-7 (FIG. 17), Li9-1 (FIG. 18), Li9-4 (FIG. 19),Lii5-2 (FIG. 20), Lii10-6 (FIG. 21), Liii4-5 (FIG. 22) or GBP-TA (FIG.23).

[0010] The present invention also relates to an above defined diagnosticcomposition or a medicament, the nucleic acid sequence whose modifiedexpression is connected with a malignant tumoral disease comprising anucleic acid sequence (a) which on account of the degeneration of thegenetic code differs from an above nucleic acid sequence shown in FIGS.1 to 23 as regards the codon sequence;

[0011] (b) which hybridizes with a nucleic acid sequence according toany of FIGS. 1 to 23 or according to (a); or

[0012] (c) which is a fragment, an allelic variant or another variant ofone of the above defined nucleic acid sequences.

[0013] The term “hybridizing nucleic acid sequence” refers to a nucleicacid sequence which under normal conditions, in particular 20° C. belowthe melting point of the nucleic acid, hybridizes with a nucleic acidsequence shown in the figures. The term “hybridize” used in the presentinvention refers to conventional hybridization conditions, preferably tohybridization conditions using as a solution 5×SSPE, 1% SDS, 1×Denhardt's solution and/or having a hybridization temperature between50° C. and 70° C., preferably of 65° C. Following hybridization, a washstep is preferably carried out first with 2×SSC, 1% SDS and then with0.2×SSC at temperatures between 50° C. and 70° C., preferably of 65° C.(for a definition of SSPE, SSC and Denhardt's solution see Sambrook etal., Molecular Cloning: A Laboratory Manual, 2^(nd) edition, Cold SpringHarbor Laboratory Press, Cold Spring Harbor N.Y. (1989)). Stringenthybridization conditions, as described in Sambrook et al., supra, forexample, are preferred.

[0014] The terms “another variant” or “fragment” used in the presentinvention comprise nucleic acid sequences which differ from thesequences indicated in the figures or the above hybridizing sequences bydeletion(s), insertion(s), substitution(s) and/or other modificationsknown in the art and a fragment of the original nucleic acid sequence,respectively, the protein encoded by these nucleic acid sequences alsocomprising one or more properties described above or in the examples.Allele variants are also counted thereamong. The variants show homologyof at least 70%, at least 80%, preferably at least 90%, most preferablyat least 95%, 96%, 97%, 98% or 99% with respect to the claimedsequences. Methods of producing the above modifications in the nucleicacid sequence are known to a person skilled in the art and are describedin standard works of molecular biology, e.g. in Sambrook et al., supra.The person skilled in the art can also determine whether a proteinencoded by a nucleic acid sequence modified in this way still has thedesired biological properties. Above all in connection with diagnosticapplications and/or compositions which use one of the above nucleic acidsequences, the term “fragment” relates to a fragment which has a lengthof at least 12, preferably at least 20 and more preferably at least 25,nucleotides.

[0015] In a preferred embodiment the above defined nucleic acid moleculeis a cDNA. In another preferred embodiment, the nucleic acid sequence isa genomic DNA which is preferably derived from a mammal, e.g. a humanbeing. Screening methods based on nucleic acid hybridization permit theisolation of the genomic DNA molecules according to the invention fromany organism or derived genomic DNA libraries, probes being used whichcontain the nucleic acid sequence indicated in the figures or a fragmentthereof.

[0016] The nucleic acid sequences can also be inserted in a vector orexpression vector. A person skilled in the art is familiar with examplesthereof. In the case of an expression vector for E. coli, these are e.g.pGEMEX, pUC derivatives (e.g. pUC8), pBR322, pBlueScript, pGEX-2T, pET3band pQE-8. For the expression in yeast, e.g. pY100 and Ycpad1 have to bementioned while e.g. pKCR, pEFBOS, cDM8 and pCEV4 have to be indicatedfor the expression in animal cells. The baculovirus expression vectorpAcSGHisNT-A is especially suited for the expression in special insectcells. In a preferred embodiment, the nucleic acid is functionallylinked in the vector with regulatory elements permitting the expressionthereof in prokaryotic or eukaryotic host cells. Such vectors containalong with the regulatory elements, e.g. a promoter, typically areplication origin and specific genes permitting the phenotypicselection of a transformed host cell. The regulatory elements for theexpression in prokaryotes, e.g. E. coli, comprise the lac-, trp promoteror T7 promoter and those for the expression in eukaryotes comprise theAOX1 or GAL1 promoter in yeast and the CMV, SV40, RVS-40 promoter, CMVor SV40 enhancer is used for the expression in animal cells. Furtherexamples of suitable promoters are the metallothionein I and thepolyhedrin promoters.

[0017] Suitable vectors are in particular also expression vectors basedon T7 for the expression in bacteria (Rosenberg et al., Gene 56 (1987),125) or pMSXND for the expression in mammalian cells (Lee and Nathans,J. Biol. Chem. 263 (1988), 3521).

[0018] General methods known in this special field can be used forconstructing vectors or plasmids containing the above nucleic acidsequences and suitable control sequences. These methods comprise e.g. invitro recombination methods, synthetic methods and in vivo recombinationmethods, as described in Sambrook et al., supra, for example.

[0019] Host organisms can be transformed with the above describedvectors. These transformants comprise bacteria, yeasts, insect andfurther animal cells, preferably mammalian cells. The E. coli strainsHB101, DH1, x1776, JM101, JM109, BL21, XL1Blue and SG 13009, the yeaststrain Saccharomyces cerevisiae and the animal cells L, 3T3, FM3A, CHO,COS, Vero, HeLa as well as the insect cells sf9 are preferred. Methodsof transforming these host cells for the phenotypic selection oftransformants and for the expression of the above nucleic acid sequencesusing the above described vectors are known in this special field.

[0020] The above mentioned nucleic acids are particularly suited asantigen-coding structure for therapeutic purposes. The objective is tostimulate the immune system and eliminate tumor cells which areidentified via a nucleic acid. In this connection there are variouspossibilities, e.g. giving the patient the naked DNA by injection. Tothis end, a plasmid having a very active promoter and at least onenucleic acid according to the invention, comprising in particularse20-10, se57-1, Lg1-2, se1-1, se2-1, se2-2, se14-3, se20-7, se20-9,se33-1, se37-2, L14-2, L15-7, Li9-1, Li9-4, Lii5-2, Lii10-6, Liii4-5 orGBP-TA, is introduced e.g. into the muscle or intradermally byinjection.

[0021] Furthermore, the nucleic acid sequence can be inserted in thevector for the purpose of recombinant production and also, usingvectors, to introduce the DNA by injection into patients where this DNAencodes an antigen for therapeutic purposes. The objective is that thecells take up the plasmid, produce antigens, present individual peptidesvia HLA molecule, thus causing a cytotoxic T-cell immune response whichshall then result in combating tumor cells. This procedure is generallydescribed in Conry et al., Clinical Cancer Research 4, pp. 2903-2912(1998). The gene gun method is an alternative which is described inFynan et al., Proc. Natl. Acad. Sci. U.S.A. 90, pp. 11478-11482 (1993).Here, the nucleic acid is introduced into in vivo antigen-presentingcells (APCs), e.g. dendritic cells, by means of a vector for theHLA-presentation of the encoded protein. The vector containing thenucleic acid according to the invention can in this case be injecteddifferently:

[0022] a) Lipid- or liposome-packed DNA or RNA, e.g. generally describedby Nabel et al., Proc. Natl. Acad. Sci. U.S.A. 93, pp. 15388-15393(1996).

[0023] b) Using a bacterium as a transport vehicle for the expressionvector. Suitable bacteria are e.g. (attenuated) listerias [e.g. Listeriamonocytogenes], salmonella strains [e.g. Salmonella spp.]. Thistechnique is generally described by Medina et al., Eur.

[0024] J. Immunol. 29, pp. 693-699 (1999) as well as Guzman et al., Eur.J. Immunol. 28, pp. 1807-1814 (1998).

[0025] Reference is also made to WO 96/14087; Weiskirch et al.,Immunological Reviews 158, pp. 159-169 (1997) and US-A-5,830,702.

[0026] c) By means of gene gun (Williams et al., Proc. Natl.

[0027] Acad. Sci. U.S.A. 88, pp. 2726, 2730, 1991).

[0028] In a preferred embodiment, the vector containing the abovenucleic acid sequences is a virus, e.g. an adenovirus, vaccinia virus oran AAV virus, which is of use for a gene therapy. Retroviruses areparticularly preferred. Examples of suitable retroviruses are MoMuLV,HaMuSV, MuMTV, RSV or GaLV. Furthermore, the above mentioned viruses andthe fowlpox virus, canarypox virus, influenza virus or sindbis virus canalso be used as a basis for a vaccine. Such new vaccines which whenadministered to the patient give anti-tumor immunity, are described e.g.in N. Restifo, Current Opinion in Immunology 8, pp. 658-663 (1996) orYing et al., Nature Medicine 5(7), p. 823 et seq., (1999). For thepurpose of genetic engineering, the above nucleic acid sequences canalso be transported to the target cells in the form of colloidaldispersions. They comprise e.g. liposomes or lipoplexes (Mannino et al.,Biotechniques 6 (1988), 682).

[0029] In order to produce tumor immunity it is also preferred totransfect an above nucleic acid sequence in antigen-presenting cells andintroduce it into the patient by injection. Here, a plasmid isintroduced in vitro into an antigen-presenting cell (APCs), e.g.dendritic cells, which then produce antigens and present individualpeptides via HLA molecules. In this connection, the plasmid DNA can beintroduced into the antigen-presenting cells in various ways:

[0030] (a) as a naked DNA, e.g. by means of gene gun or electroporation;

[0031] (b) as a lipid- or liposome-packed DNA or RNA (Nair et al.,Nature Biotechnology 16, p. 364 et seq. (1998));

[0032] (c) with a virus as a vector (Kim et al., J. of Immunotherapy20(4), pp. 276-286 (1997));

[0033] (d) with a bacterium as a transport vehicle for the expressionvector (Medina et al., Eur. J. Immunol. 29, pp. 693-699 (1999); Guzmanet al., Eur. J. Immunol 28, pp. 1807-1814 (1998)).

[0034] It is also possible to prepare the protein encoded by an abovenucleic acid and correlated with the presence of a malignant tumoraldisease. The method preferably used for this purpose comprises culturingthe above described host cells under conditions which permit theexpression of the protein (preferably stable expression) and collectingthe protein from the culture. Suitable methods for the recombinantproduction of the protein are generally known (see e.g. Holmgren, Annu.Rev. Biochem. 54 (1985), 237; LaVallie et al., Bio/Technology 11 (1993),187; Wong, Curr. Opin. Biotech. 6 (1995), 517; Romanos, Curr. Opin.Biotech. 6 (1995), 527; Williams et al., Curr. Opin. Biotech. (1995),538; and Davies, Curr. Opin. Biotech. 6 (1995), 543). Suitablepurification methods (e.g. preparative chromatography, affinitychromatography, e.g. immunoaffinity chromatography, HPLC, etc.) are alsogenerally known. In this connection, it should be noted that the abovementioned protein can be modified according to conventional methodsknown in this special field. These modifications comprise substitutions,insertions or deletions of amino acids which modify the structure of theprotein while substantially maintaining its biological activity. Thesubstitutions preferably comprise “conservative” substitutions of aminoacid residues, i.e. substitutions by biologically similar residues, e.g.the substitution of a hydrophobic residue (e.g. isoleucine, valine,leucine, methionine) by another hydrophobic residue, or the substitutionof a polar residue by another polar residue (e.g. arginine by lysine,glutamic acid by asparagic acid, etc.). Deletions may results in thepreparation of molecules which are markedly reduced in size, i.e. whichlack e.g. amino acids at the N-terminus or C-terminus.

[0035] Injections of at least one of the proteins or one or several ofthe peptides derived therefrom are also suited for the desiredanti-tumor vaccination. For this purpose, HLA-dependent peptidefragments are determined from the sequence of the protein according tothe invention by means of either corresponding computer programs orexperiments (e.g. phagocytotic picture of the whole protein, thereafteranalysis of the presenting molecules). They are produced artificially bymeans of methods known to the person skilled in the art and then giventhe patient by injection (where necessary, with immunesystem-stimulating factors, e.g. interferons, interleukins, etc.). Theobjective behind this treatment is that the APCs take up the peptides,present them, thus stimulating in vivo the production of tumor-specificcytotoxic T-cells. This principle was generally described by Melief etal., Current Opinion in Immunology 8, pp. 651-657 (1996).

[0036] Just as described above, in place of the vector the above proteinor fragment thereof can also be loaded in vitro onto APCs. The loadedcells are then introduced into the patient, e.g. into the lymph nodes,by injection and directly provide for the stimulation and proliferationof tumor-specific cytotoxic T-cells (Nestle et al., Nature Medicine4(3), p. 328 et seq. (1998); Schadendorf et al., in: Burg, Dummer,Strategies for Immunointerventions in Dermatology, Springer Verlag,Berlin Heidelberg, pp. 399-409, 1997). Regarding the vaccination it maybe advantageous to modify individual amino acids with respect to thewild-type antigen, as described above, since under certain circumstancesthis might increase the bond and improve the effectiveness (Clay et al.,The Journal of Immunology 162, pp. 1749-1755, 1999).

[0037] As regards the above therapeutic measures particularly preferredis at least one nucleic acid sequence which comprises the nucleic acidsequence se20-10 (FIG. 2), se57-1 (FIG. 3), Lg1-2 (FIG. 5), se1-1 (FIG.6), se2-1 (FIG. 7), se2-2 (FIG. 8), se 14-3 (FIG. 9), se20-7 (FIG. 11),se20-9 (FIG. 12), se33-1 (FIG. 13), se37-2 (FIG. 14), L14-2 (FIG. 16),L15-7 (FIG. 17), Li9-1 (FIG. 18), Li9-4 (FIG. 19), Lii5-2 (FIG. 20),Lii10-6 (FIG. 21), Liii4-5 (FIG. 22) or GBP-TA or a protein encodedthereby or a fragment thereof.

[0038] The present invention also relates to antibodies which detectspecifically the above described proteins (tumor antigens). Theantibodies may be monoclonal, polyclonal or synthetic antibodies orfragments thereof, e.g. Fab, Fv or svFv fragments. They are preferablymonoclonal antibodies. For the preparation thereof it is favorable toimmunize animals—particularly rabbits or chickens for a polyclonalantibody and mice for a monoclonal antibody—with an above (fusion)protein or with fragment(s) thereof. Further “boosters” of the animalscan be effected with the same (fusion) protein or with fragmentsthereof. The polyclonal antibody may then be obtained from the animalserum or egg yolk. The antibodies according to the invention can beprepared according to standard methods, the protein encoded by the abovementioned nucleic acid sequences or a synthetic fragment thereof servingas an immunogen. Monoclonal antibodies may be prepared by the methoddescribed by Kohler and Milstein (Nature 256 (1975), 495) and Galfré(Meth. Enzymol. 73 (1981), 3), for example, murine myeloma cells beingfused with spleen cells derived from immunized mammals. These antibodiescan be used for the immunoprecipitation of the above discussed proteinsor for the isolation of related proteins from cDNA expression libraries,for example. The antibodies can be bound in immunoassays in the liquidphase or to a solid carrier, for example. Here, the antibodies may belabeled in different ways. Suitable markers and labeling methods areknown in the special field. Examples of immunoassays are ELISA and RIA.

[0039] Furthermore, along with their diagnostic suitability theantibodies can also be used therapeutically. Here, e.g. a proteinencoded by the above nucleic acid sequences serves as a target forbispecific antibodies. Reference is made in this connection toKastenbauer et al., Laryngorhinootologie 78(1), pp. 31-35 (1999) and Caoet al., Bioconj. Chem. 9(6), pp. 635-644 (1998). The antibodiesaccording to the invention are suited to catch antigen which isoverexpressed in tumors, for example, so as to inhibit the tumor growth,since there is reference that in some cases the occurrence of tumorantigens does not only indicate the presence of malignant tumors butactively promotes the tumor growth.

[0040] It is also possible to inhibit the translation of the abovenucleic acid sequences which have increased expression in tumors usingantisense DNA (RNA) or ribozymes so as to exert specifically atherapeutic effect on these nucleic acid sequences or genes. In thecorresponding tumor cells, RNA/DNA hybrids form which prevent thetranscription in this way and—in the case of the antisenseRNA—simultaneously effect a degradation of the hybrids (and thus theRNA) by RNase H (Scanlon et al., The Faseb Journal 9, pp. 1288-1296,1995).

[0041] The present invention thus relates to a medicament or adiagnostic composition which contains the above described nucleic acidsequences, vectors, proteins, antibodies, etc., or combinations thereofand to the use thereof for diagnosis and/or therapy. They are usedpreferably for the diagnosis or treatment of malignant tumoral diseases,in particular CTCL. The provision of a vaccination agent which, asdescribed above, is based on either the nucleic acid sequence or theprotein/peptide is preferred. Herein, the diagnostic composition issuited to detect a malignant tumoral disease and also to carry out afollow-up, e.g. to accompany a therapy.

[0042] The above medicaments additionally contain, where appropriate, apharmaceutically compatible carrier. Suitable carriers and theformulation of such medicaments are known to the person skilled in theart. Suitable carriers are e.g. phosphate-buffered common saltsolutions, water, emulsions, e.g. oil/water emulsions, wetting agents,sterile solutions, etc. The medicaments can be administered orally orparenterally. The methods for the parenteral administration comprise thetopical, intra-arterial, intramuscular, subcutaneous, intramedullary,intrathekal, intraventricular, intravenous, intraperitoneal orintranasal administration. The suitable dosage is determined by theattending physician and depends on various factors, e.g. the patient'sage, sex and weight, the disease stage, the kind of administration, etc.

[0043] A above nucleic acid sequence can also be used as a probe toisolate DNA molecules which originate from another species or anotherorganism, for example, and code for a protein having the same biologicalactivity. For this purpose, the probe preferably has a length of atleast 20, in particular preferably at least 25 bases. Suitable detectionmethods based on the hybridization are known to the person skilled inthe art, e.g. Southern or Northern blot. The person skilled in the artis also familiar with suitable labelings for the probe, which comprisee.g. labeling with radioisotopes, bioluminescence, chemiluminescence,and fluorescence markers, metal chelates, enzymes, etc.

[0044] In addition, this can also be made by PCR (Wiedmann et al., PCRMethods Appl. 3, pp. 551-564 (1994); Saiki et al., Nature 324, pp.163-166 (1986)) or ligase chain reaction (LCR) (Taylor et al., Curr.Opin. Biotechnol. 6, pp. 24-29 (1995); Rouwendal et al., Methods Mol.Biol., pp. 149-156 (1996)), the primers being derived from the sequencein the figures and suitable primers (as regards length, complementaritywith respect to the matrix, the region to be amplified, etc.) beingdesignable by the person skilled in the art according to common methods.

[0045] Besides, the present invention relates to a method for thediagnosis of malignant tumoral diseases, in vitro, the above nucleicacid sequences or fragments thereof being used as a probe.

[0046] With respect to the diagnostic method it is preferred to providethe nucleic acids and/or proteins in the form of an ELISA kit, a proteinchip, nucleic acid chip or membrane loaded with DNA, RNA or protein.

[0047] In connection with the above-mentioned method, it is possible touse methods known to the person skilled in the art as regards thepreparation of DNA or RNA from biological samples, the restrictiondigestion of the DNA, the separation of the restriction fragments ongels separating according to size, e.g. agarose gels, the preparationand labeling of the probe and the detection of hybridization, e.g. bymeans of Southern blot or in situ hybridization.

[0048] This diagnostic method is preferably a method comprising thesteps of:

[0049] isolating nucleic acid from the patient,

[0050] carrying out LCR or PCR with suitable primers or a hybridizationanalysis with one or more suitable probes based on a nucleic acidsequence of the figures;

[0051] detecting an amplified product or a hybridization as anindication of the presence (or absence) of a tumoral disease (as afunction of whether the respective nucleic acid sequence is expressed toa greater or lesser extent as compared to the control tissue (or is notexpressed) in the tumor).

[0052] Here, primers are used which flank an above discussed nucleicacid sequence or suitable partial regions. For this purpose,amplification products of mRNA from the respective tissue are ofdiagnostic significance, which products differ as regards the occurrenceof tumor-specific, in particular CTCL-specific, bands from theamplification products of mRNA from healthy tissue.

[0053] In an alternative preferred embodiment, a method can be usedwhich comprises the steps of:

[0054] isolating RNA from the patient,

[0055] carrying out a Northern blot analysis with one or more suitableprobes,

[0056] comparing the concentration and/or length of the correspondingmRNA of the patient's sample with an mRNA from a healthy person, anincreased or lowered concentration of mRNA (as a function of thecorresponding marker; see Table 4) as compared to the control mRNA fromnormal tissue being an indication of a tumoral disease, in particularCTCL.

[0057] In this method, it is possible to use methods known to the personskilled in the art as regards the preparation of whole RNA orpoly(A)+RNA from biological samples, the separation of the RNAs on gelsseparating according to size, e.g. denaturing agarose gels, thepreparation and labeling of the probe and the detection via Northernblot.

[0058] In another alternative embodiment, a possible tumoral disease canalso be diagnosed by a method comprising the steps of:

[0059] obtaining a cell sample from the patient,

[0060] contacting the resulting cell sample with one or more proteinsencoded by the nucleic acid sequences according to the invention orfragments thereof as probe(s) under conditions permitting the binding ofantibodies, the presence of antibodies in the cell sample being anindication of a tumoral disease, in particular CTCL.

[0061] This detection can also be carried out using standard methodswith which the person skilled in the art is familiar. He also knows celldigestion methods which permit the isolation of the antibodies in a waysuch that they can be contacted with the antigen. The bound antibody ispreferably detected by means of immunoassays, e.g. Western blot, ELISA,FACS or RIA or immunohistochemical methods. It is preferably carried outby means of ELISA or dot blot. For establishing an ELISA, the abovenucleic acid sequences or fragments thereof can be cloned intoexpression plasmids and the corresponding proteins can be preparedrecombinantly, preferably as fusion proteins with a His-Tag, whichfacilitates the purification thereof. The proteins are then applied tomembranes or other suitable surfaces, optionally fixed and incubatedwith adequately diluted patient serums. After the common wash steps, anincubation is carried out with a secondary labeled antibody according toroutine methods for detecting the bound patient's antibodies. Thepatient serums are preferably incubated with a plurality of markerproteins (antigens) since the detection of the presence (or absence) ofdifferent antibodies better indicates the underlying tumoral disease andpossibly enables a classification according to the disease stage.

[0062] The present invention also relates to a kit for carrying out thediagnostic method according to the invention, which contains theantibody according to the invention or a fragment thereof, an aboveprotein (or a peptide derived therefrom), a nucleic acid sequenceaccording to the invention (as a probe) or a primer suited for PCR orLCR, for example, and based on the nucleic acid sequences according tothe invention (or a primer pair), optionally in combination with asuitable detection means.

[0063] Depending on the development of the diagnostic method to becarried out with the kit according to the invention, the compoundscontained in the kit (nucleic acid molecules, proteins, antibodies orfragments thereof) can be immobilized on a suitable carrier, i.e. in theform of a chip or be bound on a membrane.

[0064] All of the above mentioned proteins are detected serologicallyonly by antibodies from the serums of tumor patients but not from theserums of control persons and are thus serologically tumor-specific.Since this specificity is not limited to a tumor type these proteins andantibodies are very well suited to make a distinction between malignityand non-malignity at all. An advantage in this connection is to carryout a study with more than one of the above mentioned tumor markers,i.e. a combination of tumor markers, and chose a therapeutic approachdependent thereon. This means that the medicament according to theinvention should also contain more than one of the above mentionednucleic acids, proteins or antibodies.

[0065] The invention is now described in more detail by means of thefigures in which:

[0066]FIG. 1 shows the nucleic acid sequence of se2-5 and an ORF derivedtherefrom,

[0067]FIG. 2 shows the nucleic acid sequence of se20-10 and an ORFderived therefrom,

[0068]FIG. 3 shows the nucleic acid sequence of se57-1 and an ORFderived therefrom,

[0069]FIG. 4 shows the nucleic acid sequence of se70-2 and an ORFderived therefrom,

[0070]FIG. 5 shows the nucleic acid sequence of Lg1-2 and an ORF derivedtherefrom,

[0071]FIG. 6 shows the nucleic acid sequence of se1-1 and an ORF derivedtherefrom,

[0072]FIG. 7 shows the nucleic acid sequence of se2-1 and an ORF derivedtherefrom,

[0073]FIG. 8 shows the nucleic acid sequence of se2-2 and an ORF derivedtherefrom,

[0074]FIG. 9 shows the nucleic acid sequence of se14-3 and an ORFderived therefrom,

[0075]FIG. 10 shows the nucleic acid sequence of se20-4 and an ORFderived therefrom,

[0076]FIG. 11 shows the nucleic acid sequence of se20-7 and an ORFderived therefrom,

[0077]FIG. 12 shows the nucleic acid sequence of se20-9 and an ORFderived therefrom,

[0078]FIG. 13 shows the nucleic acid sequence of se33-1 and an ORFderived therefrom,

[0079]FIG. 14 shows the nucleic acid sequence of se37-2 and an ORFderived therefrom,

[0080]FIG. 15 shows the nucleic acid sequence of se89-1 and an ORFderived therefrom,

[0081]FIG. 16 shows the nucleic acid sequence of L14-2 and an ORFderived therefrom,

[0082]FIG. 17 shows the nucleic acid sequence of L15-7 and an ORFderived therefrom,

[0083]FIG. 18 shows the nucleic acid sequence of Li9-1 and an ORFderived therefrom,

[0084]FIG. 19 shows the nucleic acid sequence of Li9-4 and an ORFderived therefrom,

[0085]FIG. 20 shows the nucleic acid sequence of Lii2-5 and an ORFderived therefrom,

[0086]FIG. 21 shows the nucleic acid sequence of Lii10-6 and an ORFderived therefrom,

[0087]FIG. 22 shows the nucleic acid sequence of Liii4-5 and an ORFderived therefrom,

[0088]FIG. 23 shows the nucleic acid sequence of GBP-TA and an ORFderived therefrom,

[0089]FIG. 24 shows the localization of GBP-TA, GBP-Ta_(short) and Lg1-2on chromosome 1p22.3. The primers used for distinguishing the splicingvariants are drawn in.

[0090] Primer set I: tgt tgt aga tca ctt caa ggt gc (forw.)

[0091] cca tat cca aat tcc ctt ggt gtg ag (re.) annealing temperature63° C.

[0092] Primer set II: aga agg aag aaa ctc caa aca cat cc (forw.)

[0093] cca tat cca aat tcc ctt ggt gtg ag (re.) annealing temperature48° C.

[0094] The invention is now described below with reference to theexamples.

[0095] As to the methods used reference is made along with the methodsdescribed in Example 1 to Sambrook, J. Fritsch, E. F. and Maniatis, T.(Molecular cloning; a laboratory manual; second edition; Cold SpringHabor Laboratory Press, 1989) and Current Protocols in Molecular Biology(John Wiley and Sons, 1994-1998), the below methods, in particular thescreening of cDNA libraries, preparation of DNA or RNA, PCR, RT-PCR orNorthern blot, being sufficiently known to, and mastered by, the personskilled in the art.

EXAMPLE 1 General Method (A) Tissues and Serums

[0096] Serums and tumor tissues were obtained in diagnostic ortherapeutic routine methods with the patient's consent (and thepermission of the competent ethics committee). The tissues and sera werestored at −20° C. or −80° C.

(B) Preparation of cDNA Libraries

[0097] mRNA was extracted from testis samples using a kit for RNAisolation (RNeasy midi kit; Qiagen, Hilden, Germany) and then a kit formRNA isolation (oligotex mRNA kit; Qiagen) in accordance with themanufacturer's recommendations. A total of 10.4 μg mRNA were used forthe construction of the λ-ZAP expression library (UNI-ZAP# XR customcDNA library; Stratagene, La Jolla, Calif., U.S.A.). The cDNA libraryconsisted of 10⁶ primary recombinants having an insertion length of over0.4 kbp and was amplified to give 10¹⁰ plaque-forming units (pfu). 4.8μg mRNA from different samples of cutaneous T-cell and B-cell lymphomaswere used for the construction of the CTCL library. The number ofprimary recombinants was 6×10⁷. The procedure was analogous to thepreviously described procedure used in the case of the testis library.

(C) Immunoscreening

[0098] Immunoscreening was carried out as described in Sahin et al.(PNAS U.S.A. 92 (1995), 11810-11813) and Tureci et al. (Cancer Res. 56(1996), 4766-4772). All of the serums were diluted in Tris-bufferedsaline (TBS with 0.2% milk powder, pH 7.5) and pre-absorbed with E. coliproteins (broken up mechanically or lyzed by phages without insertion).E. coli transduced using recombinant λ-ZAP phages were plated onto NZYagar at a concentration of 2000 plaques/plate, and the expression of therecombinant proteins was induced by means ofisopropyl-β-D-thiogalactoside. The plates were incubated at 37° C.overnight and the proteins were transferred at 37° C. for 4 hours onnitrocellulose membranes and bound. The membranes were washed with TBSwhich contained Tween-20™ (0.05%), saturated with 5% milk powder in TBSand incubated with serums (either from patients or as a control fromhealthy persons) at a final concentration of 1/100. Reactive proteinswere identified with an alkaline phosphatase-coupled secondary antibody(goat anti-human IgC, Fc fragment; Dianova, Hamburg, Germany) and madevisible by means of 5-bromo-4-chloro-3-indolylphosphate and nitrobluetetrazolium. Positive phagemides were further investigated by means ofserums from patients suffering from Mycosis fungoides (n=15) and Sézarysyndrome (n=3) and healthy persons as a control (n=10). Positivephagemides were subcloned for monoclonality and subjected to an in vivoexcision of the pBluescript plasmid (in accordance with the protocolfrom the manufacturer of Genbank, Stratagene, La Jolla, Calif., U.S.A.).DNA was isolated in accordance with the manufacturer's protocol (QIAprepspin miniprep; Qiagen). The size of the insertions was analyzed bySmaI/KpnI cleavage and gel electrophoresis. Sequencing was carried outby means of an automatic fluorescence sequencing device (model 377;Perkin-Elmer/Applied Biosystems, Forster System, Calif., U.S.A.) and theDye-Terminator method in accordance with the manufacturer's instructions(ABI PRISM Big Dye Ready Reaction Terminator Cycle Sequencing Kit;Perkin-Elmer). Primers were synthesized chemically. The sequences of theclones were completely determined on both complementary strands.

(D) Tumor Tissues and Cell Lines

[0099] Tissue samples obtained from 17 CTCL patients served as a sourcefor the preparation of tumor cDNA: 13 Mycosis fungoides (stages Ib toIVb), mainly IIb), 2 Sézary syndromes (stage III), 1 T-zone lymphoma(stage IVb) and 1 CD30+ CTCL (stage IIb). Furthermore, cDNAs of thefollowing 4 CTCL cell lines were prepared: My-La (Mycosis fungoides;Kaltoft et al., In Vitro Cell Dev. Biol. 28a (1992), 161-167), SeAx(Sézary syndrome; Kaltoft et al., Arch. Dermatol. Res. 280 (1988),264-267), HH (lymphomatoid papulosis; ATCC No.: CRL-2105) and HuT-78(Sézary syndrome; ATCC No.: TIB-161). Besides, cDNA was prepared fromsix leukemia cell lines (ARA-10, Jurkat, KG1, K562, Nalm-2 and SKW6.4and 22 melanoma cell lines.

[0100] For analyzing the tissue distribution within normal tissues,control cDNAs were used in detail, which also comprised three fields ofcommercially available cDNAs (all from Clontech, Calif., U.S.A.): humanmultiple tissue cDNA field I, field II and human fetal MTC field. Inaddition, different commercially available whole RNAs for thepreparation of further control cDNAs were produced by means of the abovedescribed method. Finally, cDNAS of three activated CD8+ T-cell lines(Möller et al., British Journal of Cancer 77 (1998), 1907-1916) alsoserved as control T-cells.

(E) RT-PCR

[0101] On account of the limited amount of RNA, RT-PCR was preferablyused for studying the identified sequences within different normaltissues and tumor tissues. In selected cases, these studies werecompleted by means of Northern blot analyses. RT-PCR was carried out bymeans of “MJ Research PCT-200” (Biozym, Oldendorf, Germany) with aone-minute attachment at variable temperature and 35 cycles. All of theRT-PCRs were carried out in at least two independent experiments. As forthe rest, the RNA isolation, RT-PCR and Northern blot analyses werecarried out according to conventional standard methods and understandard conditions. The primer sequences and annealing temperatures forthe different clones are indicated in below table 1: Anneal. CloneForward Primer Reverse Primer Temp. se1-1 gca aaa gca att aga cgc tac ccac agc cct gtt ctt ctt tag c 57° C. se2-1 gta cag cag aaa gca agc aactga atg gga aat tgg att cta aag cag ttc ctt c 55° C. se2-2 cta tga atccaa gac caa agg c ctc cac ttt ggt cct tgt tag c 59° C. se2-5 acc cac gcagat ttg gaa tc agg ctg atc act ggc tgt g 59° C. se14-2 cct tat tgt acactg ggg ctt c cag aca caa gga act gaa gta acg 60° C. se14-3 cac tgc caagat aga caa gca g gct ctt atc cag gaa gtc cat g 59° C. se20-4 tac aggatc tca gac ata tct cca tg aaa tgt ctt ccc act gca taa tag tc 59° C.se20-7 taa gga aac aat tca gtc aca taa gg ctg tag ctt agc aat ttg ttcttct g 59° C. se20-9 tta tga ggc tta gaa ttt caa cca c aaa ggc ttt caaaac att ttt caa c 59° C. se20-10 gta gag atc aga gag ttg tga cat ctg tattac ttt tca ctg tta cac tgc tgg 59° C. se33-1 gcc aca gag aat gaa ccactt aac gag gga cta tca gtt gct gtt tg 60° C. se37-2 gca tct aat aga acgcta cta cca cc ctg tga gct atc acc tat cct tga g 60° C. se57-1 gtg acagtg acc aca gaa att ccc cc cac gtt tct cag agc tgc tgc tcc 63° C. se70-2gct gca cag aaa acc tta ctt gtt tcc acc ctc gta aat gca gaa atc tcc aatgcc c 56° C. se89-1 tcc aca gcc tat tgg ctc act tgg ac gcc ctt tag tgtgtc tgt aat tgg aat cag 57° C. RAP140 tcc aca gcc tat tgg ctc act tgg acgca cac act gct cct cca cct gac 57° C. L14-2 gct gct gct gtt tac aga aaggct cac gga aag tta tcc aca gct act gag gac cc 64° C. L15-7 tcc cct ccattt aat ctc caa att cac cc ctc agc att tgc cgc cgt aac tt 62° C. Li9-1gaa aac tac aaa tcc cag gag cac ctc acg aaa tat gag ctt cac cac 63° C.Li9-4 tta ctg atc gtc tgc tcc cta gag tcc atc ttc tgc tca gtc aga atccca tgc 67° C. Lg1 − 2 = tgt tgt aga tca ctt caa ggt gc cca tat cca aattcc ctt ggt gtg ag 63° C. Primer set I (GBP-TA) GBP-TA tgt tgt aga tcactt caa ggt gc cca tat cca aat tcc ctt ggt gtg ag 48° C. Primer set IILii5-2 tga gaa tga ggt ggg ggt gg tgg gga acc gga tca gga c 58° C.Lii10-6 gca tcc tac cac caa ctc gtc c agt tct gag acc gtt ctt cca cc 57°C. Liii4-5 gct gcg gac ata aat ctt aaa gc agg gtc tca ctc tga ttg cc 56°C.

(F) Northern Blot

[0102] 10 μg whole RNA are separated electrophoretically on an MOPS geland transferred to positively charged nylon membranes. The probe islabeled by means of the Roche High Primer Kit using α-³²P-dCTP. Thenon-incorporated nucleotides are removed by means of the Qiagen RemovalKit (Qiagen company, Hilden). The prehybridization is carried out at 60°C. for 1-2 hours. The hybridization is preferably carried out at 60° C.overnight. The prehybridization and hybridization solutions have thefollowing composition: 10% dextran sulfate, 1% SDS, 10× Denhardt'sreagent, 3×SSC. The subsequent wash step is carried out at 42° C. using2×SSC/0.1% for 2×30 minutes and then at 65° C. using 0.2×SSC/0.1% SDSfor 2×30 minutes. A Kodak X-Omat film is applied for an exposure time of3-10 days.

EXAMPLE 2 Screening According to Positive Clones

[0103] About 1.9×10⁶ recombinant clones of a cDNA library obtained fromnormal testis tissue were screened with the serums from patientssuffering from cutaneous T-cell lymphomas (CTCL) including Mycosisfungoides (MF) and Sézary syndrome. 28 clones representing 22 differentORFs and/or genes could be detected and they were further investigatedas regards serological reactivity and molecular distribution. Asecondary confirmation was carried out by the use of additional serumsfrom patients having a positively diagnosed Mycosis fungoides (MF)(n=15) or Sézary syndrome (n=3) and of 10 control serums from healthyvolunteers. The reactivity of the serums from the patients wasassociated with the tumor stage (maximum stage III) (Table 2). However,this was not statistically significant (X² test and Mann-Whitney Utest), presumably because of the small number of serums having advancedtumor stages. The reactivity of the patient serums ranged from 11% to71% of serums identifying recombinant clones. TABLE 2 Number of positiveclones in correlation with the tumor stage of the serum donor Primaryscreening Secondary screening Screened Patient's Number plaques NumberPlaques tumor of serums (positive/ of serums (positive/ stage usedtota)⁽¹⁾ Frequency⁽²⁾ used total) Frequency⁽²⁾ I 6  1/524,000 0.2 ×10⁻⁰⁵ 7  10/106 0.09 II 6 15/790,000 1.9 × 10⁻⁰⁵ 6 28/84 0.33 III 312/274,000 4.4 × 10⁻⁰⁵ 3 19/47 0.40 IV 2  0/270,000 0 2 11/39 0.28Total¹ 17    28/1,858,000 1.5 × 10⁻⁰⁵ 18   68/276 0.25

[0104] Primary screening of a testis cDNA library was carried outsuccessively with 17 individual serums originating from patientssuffering from tumors in the indicated stage. The number of positive andtotal plaques assayed are shown in the 3^(rd) column. During thesecondary screening every positive plaque (28) was subsequently testedwith up to 18 individual serums from different patients in the indicatedtumor stage.

[0105] The number and probability of all serological responses arecomprised with respect to the tumor stage of the patients from whichserums were withdrawn for screening a testis cDNA library. Although thedata show a greater probability as to the presence of antibodies againsttumor antigens (with the peak in stage III), these differences are notstatistically relevant. TABLE 3 Serological analyses of the identifiedclones CTCL Controls clone reactive n reactive n se1-1 50% 10 0% 5 se2-122% 18 0% 10 se2-2 33% 9 0% 8 se2-5 30% 10 0% 5 se14-3 11% 9 0% 5 se20-440% 10 0% 5 se20-7 30% 10 0% 7 se20-9 25% 8 0% 5 se20-10 11% 18 0% 10se33-1 29% 17 0% 10 se37-2 29% 17 0% 10 se57-1 33% 15 0% 9 se70-2 10% 100% 6 se89-1 44% 18 0% 9 L14-2 42% 19 0% 5 L15-7 33% 21 0% 7 Li9-1 19% 210% 5 Li9-4 57% 21 0% 6 Lg1-2 56% 16 0% 9 Lii5-2 20% 15 0% 8 Lii10-6 6%16 0% 8 Liii4-5 29% 17 0% 8

[0106] The table shows the percentage reactivity of the serums (numbern) against the tested clones in the secondary screening.

[0107] The percentages of reacting serums and total number of testedserums (n) during secondary screening are indicated. Clones se2-1 andse20-4 each show additionally one of the homologous clones since theydiffered as to their reaction pattern, presumably because of sequencedifferences.

[0108] Five antigens represent formerly unknown sequences (se2-5,se20-10, se57-1, se70-2 and Lg1-2). The RNA expression pattern, analyzedby means of RT-PCR, of the identified antigens varied between highlyrestricted and ubiquitous expression in 28 normal, 17 CTCL tumor tissuesand 33 tumor cell lines of different origins (Tables 4 and 5). TABLE 4Expression analysis by RT-PCR with antigen-specific primers and cDNAfrom different tissues and cell lines cDNA controls Primer multi-tissueactivated tumor tissue cell lines against panels⁽¹⁾ CTLs⁽²⁾ CTCL CTCLleukemia melanoma clone (n) (n = 3) (n) (n = 4) (n = 5-6) (n) se1-1 100%(17) 100%  91% (11) 100% 100% 100% (6) se2-1  4% (28)^((1,3))  0%  6%(17)  0%  0%  0% (11) se2-2 100% (18) 100%  90% (10) 100%  83%  80% (5)se2-5  94% (18)  0%  55% (11)  0% 100% 100% (11) se14-3 100% (18) 100%100% (11) 100% 100% 100% (11) se20-4 100% (18) 100%  92% (12) 100% 100%100% (11) se20-7 100% (15) 100% 100% (11) 100%  50%  80% (5) se20-9 100%(18) 100%  82% (11) 100%  83%  45% (11) se20-10  46% (28)⁽³⁾  67%  77%(13) 100% 100%  55% (11) se33-1  61% (28)⁽³⁾ 100%  75% (16) 100%  83%100% (11) se37-2 100% (16) 100%  93% (15) 100%  83%  75% (5) se57-1  21%(28)⁽³⁾  0%  6% (17)  0%  0%  0% (23) se70-2  54% (28)⁽³⁾  33%  31% (16)100% 100%  45% (22) se89-1  87% (23) 100%  75% (16) 100% 100%  73% (22)L14-2  75% (24)  33%  40% (15)  50%  60%  10% (21) L15-7  65% (26) 100% 33% (15)  50%  40%  20% (20) Li9-1  85% (26)  33%  80% (15)  75% 100% 42% (12) Li9-4  92% (26) 100%  73% (15)  75%  80%  60% (15) GBP-TA  32%(28)^((3,4))  0%  26% (19)  75%  20%  0% (23) Lii5-2  59% (22)  0%  21%(14)  25%  75%  21% (24) Lii10-6  86% (21) 100% 100% (14)  50% 100% ntLiii4-5  55% (22)  33%  29% (14) 100%  75% nt

[0109] TABLE 5 RT-PCR analyses by specific primers againstdifferentially expressed sequences and multiple tissue (MTC) cDNA Primeragainst clone: GBP-TA/- se2-1 se20-10 se33-1 se57-1 se70-2 TAshortintestines − − − + − − small intestine − + + + + −/+ fetal liver − − −− + −/+ fetal lung − − + − + − fetal spleen − − + − + −/+ fetal kidney− + + − + − fetal skeletal − − + − + − muscle fetal thymus − − − − + −/+fetal brain − − + − + − fetal heart − − + − + −/+ brain − + + − + − skin− − + − − − heart − + − − − − bone marrow − + + + − + liver − − + − − −lung − − + − − − stomach − + + − − + spleen − + + + + −/+ kidney − + +− + − ovary − − + − − − pancreas − − + − − − periph blood − − − − − −lymphocytes placenta − + + − − −/+ prostate − + + − − − skeletal muscle− − − − − − testis + + + + + − thymus − − + − + − trachea − + + + + −

[0110] Either commercially available cDNA assortments were used or cDNAwas prepared from RNA assortments (Clontech). Each sample contained cDNAfrom samples from several individuals. The skin cDNA was prepared from asingle sample. RT-PCR against GBP-TA/GB-Tashort distinguishes betweenboth variants.

EXAMPLE 3 Tumor-Specific Antigens

[0111] Six clones (represented by at least four different recombinants)were homologous to SCP-1, a protein connected with meiosis (Türeci etal. , PNAS U.S.A. 95 (1998) , 5211-5216) . Interestingly enough, theserological reactivity of different serums differed between thedifferent Scp-1 clones: clone se2-1 was determined by serums from 2/15MF patients and 2/3 patients suffering from Sézary syndrome. By means ofRT-PCR it was proved that se2-l is tumor-specific. Another clonehomologous to SCP-1 (se37-1) was identified by 3/9 MF serums and 1/3Sézary syndrome serums. This might reflect different epitopes of SCP-1,since the clones differed as regards length. Clone se33-2 also reactedwith 1/5 control serums. Interestingly enough, this clone encodedanother peptide sequence within the first reading frame, which was notpresent in the other clones homologous to SCP-1 and thus could representan autoantigen responsible for the reactivity of the control serum. ThePCR analyses were carried out using the same primers as published byTureci et al. (1998), which also perfectly fits the clones homologous toSCP-1. Of all the tested normal tissues and tumor samples and cell linesonly one testis sample and one MF sample (patient H.S.) was found whichexpressed SCP-1 mRNA. The positive result of the MF-cDNA could beconfirmed by Northern blot yielding a band of about 4.3 kb. Furthermore,the serum of the patient H.S. also reacted with se2-1 and one of theother clones homologous to SCP-1. In addition, according to Northernblot analysis clones se57-1 and L15-7 are tumor-specific.

EXAMPLE 4 (A) Antigens with Limited Expression Pattern and (B)Ubiquitously Expressed Antigens

[0112] 13 antigens with differential or ubiquitous expression (detectedby means of RT-PCR) are described below (see Tables 4 and 5).

(A)

[0113] For five new antigens (se2-5, se20-10, se57-1, se70-2 and Lg1-2)and two antigens with homologies to known genes (se33-1: NP220; se89-1:RAP140 protein correlated with retinoblastoma) a differential expressionshowed on a molecular level. The serological reactivity to these clones(defined as percentage of reactive serums during secondary screening)was 31% on the average. A minor reactivity rate showed with respect toclones se20-10 and se70-2 (2/18 and 1/18 reactive serums, respectively),whereas 71% of the serums from CTCL patients (n=14) reacted positivelywith clone se89-1. All of the 6 clones with up to 10 control serumsshowed no reaction.

[0114] It was started quantifying the RT-PCR results by means ofNorthern analyses. Such antigens which in normal tissues do not prove tobe equally expressed as compared to tumor samples are considered to bepotential therapeutic agents.

[0115] It was possible to show by means of RT-PCR analyses that these-2-5-specific m-RNA is expressed almost ubiquitously in normal tissuesbut not in activated T-cells and only in 55% of the CTCL tissue samples.In contrast therewith, the Northern blot analysis showed a limitedexpression pattern even within normal tissues. Intense signals weredetectable in kidney, esophagus and testis, weaker ones wereidentifiable in colon, small intestine, thymus, bone marrow and stomach.While in all of the positive normal tissues three bands were detectable(5.2, 5.4 and 3.9 kB), the only positive CTCL cell line SeAx showed asignal at 3.9 kb. Specific mRNAs for clones se20-10 and se57-1 werefound by means of RT-PCR in 43% of the studied control tissues and 21%thereof, respectively. Interestingly enough, the expression of the mRNAspecific to se57-1 was greatly down-regulated in all of the tumortissues and cell lines. In contrast therewith, the expression of themRNA of clone se70-2 was up-regulated (100%) as compared to normaltissues (54%) in the CTCL and leukemia cell lines, whereas the CTCLtissues and melanoma cell lines showed mean expression levels (33% and45%, respectively) . All the fetal tissues of the control tissues wereRT-PCR positive.

[0116] A differential expression showed for two antigens with homologiesto known sequences: se33-1 cDNA is homologous to NP220, a DNA-bindingprotein, and se89-1 cDNA is homologous to RAP140, aretinoblastoma-associated clone. Clone se33-1 showed 99% similarity atits 3′ end of NP220 over an overlapping distance of 3830 bp, howeverthis clone is shortened at its 5′ end, which results in a shortened ORF.The RT-PCR (using se33-1-specific primers) furnished proof of mRNA in6/8 fetal and 16/20 normal tissues (Table 5) and in CTCL tissues(12/16), activated cytotoxic T-cells and in most cell lines (Table 4).

[0117] cDNA of clone se89-1 showed 99% similarity with respect to RAP140in an overlapping region of 3444 bp and a gap of 60 bp which is locatedwithin the ORF and results in an amino acid gap of 20 amino acids.RT-PCR was carried out using different primers: first with the primercombination RAP140 (see Table 1 and Example 1), both RAP140 and se89-1being identified and three bands showing in testis-cDNA and two bandsturning up in various other cDNAs. For the specification of se89-1expression a new reverse primer (see Table 1) was designed which spansthe gap in se89-1. Using this primer together with the forward primeragainst RAP140, which also detects se89-1, only one band was amplified.The frequency of the positive cDNAs with respect to the se89-1-specificprimers did not distinguish substantially between the control tissues(79%), CTCL tissues (75%) and cell lines (CTCL and leukemia cell lines:100%, melanoma lines: 73%). By means of Northern blot analyses it waspossible to confirm the presence of mRNA specific to se89-1 within mRNAoriginating from brain, kidney, colon and testis and the CTCL line SeAx.

(B)

[0118] Six antigens homologous to known sequences (se1-1, se2-2, se14-3,se20-4, se20-9 and se37-2) proved to be expressed ubiquitously. In allof the control tissues (n=28) mRNA specific to these clones could bedetected by means of RT-PCR. In the two clones se14-3 and se20-4, all ofthe tumor tissues and cell lines were also positive in the RT-PCR. Incontrast therewith, clones se2-2, se20-7, se20-9 and se37-2 were onlyexpressed in a subgroup of the melanoma and leukemia cell lines whileCTCL tissue and CTCL cell lines showed a greater percentage of cDNAspositive in the RT-PCR.

[0119] The reactivity of patient serums with these clones was about 29%on the average, two extremes also being observable: The reactivity toclone se14-3 was revealed in 11% (1/9) and that to clone se1-1 in 50%(5/10) of the CTCL serums. Two control serums (n=10) reacted with clonese20-6 which is homologous to clone se20-4. In connection with se20-6 itwas possible to show that the latter codes for a different peptide (72aa) in the first reading frame, which was not present in either se20-4or its homologous gene HRIHFB2216. The sequence analysis of these clonesand a comparison with the homologous counterparts disclosed in somecases insertions, deletions or elongations.

[0120] It should be pointed out that all of the tested clones areserologically specific.

EXAMPLE 6 Sequence Analyses as Regards Lg1-2

[0121] A number of further clones having major correspondence with Lg1-2could be isolated, which were completed in the 3′ direction (stop codonand 3′-untranslated region is available). This is shown in FIG. 24.These clones could be comprised in a gene (GBP-TA) which was assignableto the 1p22.3 chromosome. In this connection, it was possible todifferentiate between two splicing variants: GBP-TA were assigned to 12exons while exon no. 2 lacked from GBP-TA_(short).

[0122] It was possible to derive from GBP-TA a protein which has certainhomologies to the known guanylate-binding proteins GBP-1, GBP-2 and HGBP(U.S. Pat. No. 5,871,965). However, the sequence of HGBP does notcomprise exon 2.

EXAMPLE 7 Expression Analyses with Respect to GBP-TA

[0123] RT-PCR experiments were carried out as to the analysis of GBP-TAexpression. Two different primer pairs (see FIG. 24) were used fordifferentiating the two splicing variants. Here, a large number ofcontrol cDNAs were used, each prepared from a collection of tissues fromdifferent donors. While 11 control tissues were negative for bothprimers, GBP-TA_(short) was detected in 5 tissues and both variants ofGBP-TA were only found in 2 tissues (bone marrow and stomach) (Table 6).TABLE 6 Detection of GBP-TA and GBP-TA_(short) in adult control tissuesresult Control tissue Primer set I primer set II Brain, colon, heart, −− kidney, liver, ovary, lung, PMNC, prostate, testis, thymus, tracheaplacenta, small intestine − + spleen, activ. CD8 T-cells, uterus Bonemarrow, stomach + +

[0124] In contrast to the control tissues, GBP-TA was detected invarious tumor tissues by means of RT-PCR: cutaneous T-cell lymphomas(26%, n=19), tumors from the HNO region (21%, n=14) . GBP-TAshort wasfound in 20% of the HNO tumors (n=15) and 9% of the colon carcinomas(n=35) . Se57-1 was detected in 20% of the colon carcinomas (n=35) and57% of the HNO tumors (n=28).

[0125] Since RT-PCR is extremely sensitive and allows no statement onthe presence and amount of protein, the expression was checked by meansof Western blot and a GBP-TA-specific antibody. Of the RT-PCR-positivecontrols several could be tested as protein medleys in a Western blot:placenta, small intestine, spleen, fetal liver, stomach, testis, uterus.Like other control protein medleys tested (mammary gland, testis) theyalso proved to be negative, while proteins obtained from tumors (CTCL)cell lines (SeAx, MyLa, Hut-78, HH; isolation via Tristar, AGS,Heidelberg, Germany) showed a marked band of corresponding size. Thisproves that GBP-TA is suited as a specific target structure for thetherapy.

EXAMPLE 8 Preparation of Antibodies Against GBP-TA

[0126] For the preparation of a GBP-TA-specific antibody, the insert ofa clone comprising GBP-TA bases from 539 to 1991 inclusive, was clonedinto a His vector and expressed in E. coli. The recombinant protein waspurified on a nickel column, then separated in an SDS gel for furtherpurification and the corresponding band was cut out. A rabbit wasimmunized with the cut-out gel piece, whose preimmune serum did notreact with the antigen.

[0127] Immunization Protocol for Polyclonal Antibodies in Rabbits

[0128] 600 μg of purified KLH-coupled peptide in 0.7 ml PBS and 0.7 mlcomplete or incomplete Freund's adjuvant are used per immunization:

[0129] Day 0: 1^(st) immunization (complete Freund's adjuvant)

[0130] Day 14:2^(nd) immunization (incomplete Freund's adjuvant; icFA)

[0131] Day 28: 3^(rd) immunization (icFA)

[0132] Day 56: 4^(th) immunization (icFA)

[0133] Day 80: bleeding to death.

[0134] The rabbit serum is tested in an immunoblot. For this purpose, apeptide used for the purpose of immunization is subjected to SDSpolyacrylamide gel electrophoresis and transferred to a nitrocellulosefilter (cf. Khyse-Andersen, J., J. Biochem. Biophys. Meth. 10 (1984),203-209). The Western blot analysis was carried out as described inBock, C.-T. et al., Virus Genes 8, (1994), 215-229. For this purpose,the nitrocellulose filter is incubated with a first antibody at 37° C.for one hour. This antibody is the rabbit serum (1:10000 in PBS). Afterseveral wash steps using PBS, the nitrocellulose filter is incubatedwith a second antibody. This antibody is an alkaline phosphatase-coupledmonoclonal goat anti-rabbit IgG antibody (Dianova company) (1:5000) inPBS. 30 minutes of incubation at 37° C. are followed by several washsteps using PBS and subsequently by the alkaline phosphatase detectionreaction with developer solution (36 μM5′-bromo-4-chloro-3-indolylphosphate, 400 μM nitroblue tetrazolium, 100mM Tris-HCl, pH 9.5, 100 mM NaCl, 5 mM MgCl₂) at room temperature untilbands become visible.

[0135] It shows that polyclonal antibodies according to the inventioncan be prepared.

EXAMPLE 9 ELISA

[0136] A GBP-TA insert the same as that used for the antibody collection(bases no. 539 to 1991 inclusive of GBP-TA) was cloned into a pGEXvector, expressed recombinantly and used in a GST-ELISA. The ELISAsystem used follows Sehr et al. (J. of Immunol. Meth. 2001, 253,153-162). For this purpose, glutathione-casein-coated ELISA plates wereloaded with the fusion protein and then serums from CTCL patients andcontrol persons were tested for the presence of specific antibodies. Itturned out that 17% of the CTCL serums (n=60) and only 2% of the controlserums (n=99) reacted with the GST-GBP-TA fusion protein.

[0137] The ELISA is suited for all the indicated marker antigens fordiagnostic purposes, for a prognostic estimation and for a follow-up.

1 93 1 2363 DNA Homo sapiens 1 tgaatacgca attagaactt tcagaacaacttaaatttca gaacaactct gaagataatg 60 ttaaaaaact acaagaagag attgagaaaattaggccagg ctttgaggag caaattttat 120 atctgcaaaa gcaattagac gctaccactgatgaaaagaa ggaaacagtt actcaactcc 180 aaaatatcat tgaggctaat tctcagcattaccaaaaaaa tattaatagt ttgcaggaag 240 agcttttaca gttgaaagct atacaccaagaagaggtgaa agagttgatg tgccagattg 300 aagcatcagc taaggaacat gaagcagagataaataagtt gaacgagcta aaagagaact 360 tagtaaaaca atgtgaggca agtgaaaagaacatccagaa gaaatatgaa tgtgagttag 420 aaaatttaag gaaagccacc tcaaatgcaaaccaagacaa tcagatatgt tctattctct 480 tgcaagaaaa tacatttgta gaacaagtagtaaatgaaaa agtcaaacac ttagaagata 540 ccttaaaaga acttgaatct caacacagtatcttaaaaga tgaggtaact tatatgaata 600 atcttaagtt aaaacttgaa atggatgctcaacatataaa ggatgagttt tttcatgaac 660 gggaagactt agagtttaaa attaatgaattattactagc taaagaagaa cagggctgtg 720 taattgaaaa attaaaatct gagctagcaggtttaaataa acagttttgc tatactgtag 780 aacagcataa cagagaagta cagagtcttaaggaacaaca tcaaaaagaa atatcagaac 840 taaatgagac atttttgtca gattcagaaaaagaaaaatt aacattaatg tttgaaatac 900 agggtcttaa ggaacagtgt gaaaacctacagcaagaaaa gcaagaagca attttaaatt 960 atgagagttt acgagagatt atggaaattttacaaacaga actgggggaa tctgctggaa 1020 aaataagtca agagttcgaa tcaatgaagcaacagcaagc atctgatgtt catgaactgc 1080 agcagaagct cagaactgct tttactgaaaaagatgccct tctcgaaact gtgaatcgcc 1140 tccagggaga aaatgaaaag ttactatctcaacaagaatt ggtaccagaa cttgaaaata 1200 ccataaagaa ccttcaagaa aagaatggagtatacttact tagtctcagt caaagagata 1260 ccatgttaaa agaattagaa ggaaagataaattctcttac tgaggaaaaa gatgatttta 1320 taaataaact gaaaaattcc catgaagaaatggataattt ccataagaaa tgtgaaaggg 1380 aagaaagatt gattcttgaa cttgggaagaaagtagagca aacaatccag tacaacagtg 1440 aactagaaca aaaggtaaat gaattaacaggaggactaga ggagacttta aaagaaaagg 1500 atcaaaatga ccaaaaacta gaaaaacttatggttcaaat gaaagttctc tctgaagaca 1560 aagaagtatt gtcagctgaa gtgaagtctctttatgagga aacaataaac tcagttcaga 1620 aaaaaaaaca gttgagtagg gatttggaggtttttttgtc tcaaaaagaa gatgttatcc 1680 ttaaagaaca tattactcaa ttagaaaagaaacttcagtt aatggttgaa gagcaagata 1740 atttaaataa actgcttgaa aatgagcaagttcagaagtt atttgttaaa actcagttgt 1800 atggttttct taaagaaatg ggatcagaagtttcagaaga cagtgaagag aaagatgttg 1860 ttaatgtcct acaggcagtc ggtgaatccttggcaaaaat aaatgaggaa aaatgcaacc 1920 tggcttttca gcgtgatgaa aaagtattagagttagaaaa agagattaag tgccttcaag 1980 aagagagtgt agttcagtgt gaagaacttaagtctttatt gagagactat gagcaagaga 2040 aagttctctt aaggaaagag ttagaagaaatacagtcaga aaaagaggcc ctgcagtctg 2100 atcttctaga aatgaagaat gctaatgaaaaaacaaggct tgaaaatcag aatcttttaa 2160 ttcaagttga agaagtatct caaacatgtagcaaaagtga aatccataat gaaaaagaaa 2220 aatgttttat aaaggaacat gaaaacctaaagccactact agaacaaaaa gaattacgag 2280 ataggagagc agagttgata ctattaaaggattccttagc aaaatcacct tactgtaaaa 2340 aatgatacct ctgtcttcag taa 2363 23962 DNA Homo sapiens 2 aattcggcac gaggatgagt atagggctgt ttcttgcagggttctttcga aattattgct 60 aggttgactt ttaactaaat ccaagtgatg ttatttgtaatgtagtactt aaatgttttt 120 cttgttgttt tagccaaaac tggacaagcc aaggcatctgtagccaaagt aaacaaatct 180 acagggaaat cagcaagttc tgtaaaatct gtggtaacggtagctgttaa aggtaataaa 240 gcttcaatca aaacagcaaa atctggtgga aagaagtctctagaagccaa aaagactggg 300 aatgtcaaaa acaaagactc taacaaacct gtgactataccagaaaactc tgaaataaag 360 accagtattg aagtcaaagc cactgaaaac tgtgctaaagaagctatttc tgatgctgct 420 ttggaggcca cagagaatga accacttaac aaggaaacagaagaaatgtg tgtgatgctt 480 gtctctaatt tgcctaataa aggatattct gtagaagaagtttatgactt agcaaaacca 540 tttggtggtt taaaggatat cttgatttta tcatctcataaaaaggcata tatagaaata 600 aatagaaaag ctgctgagtc tatggtaaaa ttttatacctgcttcccagt attgatggat 660 ggaaatcaac tctcaataag tatggctcct gaaagcatgaatataaaaga tgaggaagct 720 atatttataa ccttggtaaa agaaaatgac ccagaggcaaacatagatac aatttatgat 780 cgatttgtac atcttgataa tttaccggaa gatggacttcagtgtgtact ttgtgttgga 840 cttcagtttg gaaaagtgga tcaccatgta ttcataagtaatagaaacaa ggcaattctt 900 cagttagata gtcctgaatc tgctcagtca atgtatagctttctgaaaca aaatccacaa 960 aatattggtg accatatgtt gacctgctca ttatctccaaagatagactt accagaggtg 1020 caaattgagc atgacccaga attagaaaaa gaaagccctggcttgaaaaa cagtccaatt 1080 gatgaaagtg aggtgcaaac agcaactgat agtccctctgttaaacctaa tgagcttgaa 1140 gaagaaagta ctcccagcat tcaaacagaa actttggtacagcaggaaga gccttgtgag 1200 gaagaagctg aaaaagcaac atgtgattct gactttgctgttgaaacttt ggagcttgaa 1260 actcaaggag aggaggtcaa agaagaaatt cctcttgtagcatccgcttc agtcagtatt 1320 gaacaattca ctgaaaatgc cgaggagtgt gctttaaatcagcagatgtt taacagtgac 1380 ttggagaaga aaggggcaga aattattaac cctaaaacagcattgttacc atctgacagt 1440 gtgtttgcag aagaaaggaa cctcaaagga attctagaagaatctccatc tgaagcagaa 1500 gatttcattt ctggaattac acagactatg gtagaagctgtagctgaagt agaaaaaaat 1560 gaaactgttt cggaaatatt gccatcaact tgtattgtgacgttagtacc aggaattccc 1620 actggggatg agaagacagt ggacaaaaag aatatttctgaaaaaaaagg taacatggat 1680 gaaaaggagg agaaggaatt taatactaag gaaaccagaatggatcttca aataggaaca 1740 gagaaggctg aaaagaatga aggtaggatg gatgcagaaaaggtggaaaa gatggcagca 1800 atgaaagaaa agcctgcaga aaacacttta ttcaaggcatacccaaataa aggagtgggt 1860 caggctaata agcctgatga aactagtaaa actagtattctggctgtatc agatgtatct 1920 agcagtaaac caagcatcaa ggctgttata gtctcttctcctaaggcaaa agctacagtt 1980 tcaaaaactg aaaatcagaa aagttttcca aaatctgtgcccagagatca aataaatgct 2040 gaaaagaaac tttcagccaa ggaatttggt ctgcttaaacccacaagtgc caggtcaggc 2100 ttggcagaaa gcagcagtaa attcaaacct actcagagcagtcttaccag aggaggcagt 2160 ggaaggatct cagccctgca aggcaagctt tctaaactggattacagaga tataacaaaa 2220 caatctcagg aaacagaggc tagaccttcc atcatgaaacgggatgacag caacaataag 2280 actttggctg agcaaaacac taagaatcct aaaagcactactggtagaag ttccaaatct 2340 aaagaggagc cattatttcc atttaatttg gatgaatttgttactgtgga tgaggttata 2400 gaagaagtga atccttctca ggccaagcag aatccactaaagggaaaaag gaaagaaact 2460 ctcaaaaatg ttcctttctc tgaacttaac ttaaagaagaaaaaggggaa aacttccact 2520 cctcgtggtg ttgagggaga actatctttt gtgacattggatgagattgg ggaagaggaa 2580 gatgcagctg cacatctagc acaagctcta gtcactgtggatgaagtaat tgatgaagaa 2640 gaactaaata tggaagaaat ggtaaaaaat tcaaattcactttttacatt agatgaatta 2700 attgaccaag atgattgcat ttcccacagt gaacctaaagatgttactgt tctgtcagtg 2760 gctgaagaac aagatctcct caaacaggaa cgcttggtaactgtggatga aattggagaa 2820 gtggaagagc tacctttgaa tgagtcagca gacataacttttgccacttt aaatactaaa 2880 ggaaatgaag gagatatcgt aagggattcc attggcttcatttcttctca ggtgcccgaa 2940 gacccttcta ctttagttac tgtagatgaa atacaagatgacagcagtga tttgcattta 3000 gtgactttgg atgaagtaac tgaagaggat gaagactctctggcggattt taacaacctt 3060 aaagaagagc ttaattttgt tactgttgat gaagttggagaggaggaaga tggagataat 3120 gatttaaaag ttgagttagc acaaagcaaa aatgaccatcccacagataa aaaagggaat 3180 agaaagaaga gagctgtgga cacaaaaaag acaaaacttgaatccttgtc ccaagtgggt 3240 ccagtaaatg agaatgttat ggaagaagat ctaaaaaccatgattgaaag acacttaaca 3300 gctaaaactc caaccaagag agttagaatt gggaaaactctgccatcaga aaaagctgtt 3360 gtgacagaac cagcaaaagg tgaagaggcc ttccagatgagtgaagttga tgaggaatct 3420 ggattaaagg attcagaacc agagcgaaaa cgcaagaagactgaagactc ttcttcaggc 3480 aaatcagtgg tgtctgatgt ccctgaggaa ttagactttcttgtacctaa ggctggattc 3540 ttctgtccaa tttgttccct cttctactca ggtgaaaaagcaatgacaaa tcactgcaag 3600 agtacacgtc ataagcaaaa tactgagaaa ttcatggccaagcaaagaaa ggaaaaggag 3660 cagaatgagg ctgaagaaag aagctctagg tgattgggggaaaggaaaga attcactaga 3720 aatttgttta gggtccagtt gatttgtgta tttttgttatcatttaattt gtaattttcg 3780 tttcagaagc aaatattcgt gttgtacaaa tttctgattgccctaaatgt agagagactg 3840 atggggaaag tatgatgggt ttgattttta tatcaaatcatcaggcatgg agaaatatct 3900 tttagaagtg ttaaaataaa tgttcctact gtatatttaaaataaaaaaa aaaaaaaaaa 3960 aa 3962 3 2710 DNA Homo sapiens 3 ggagatacaagtttggaagc aatcttgggg tacttaccca caaggctggt ggagaccaga 60 tcaggagaacctcagtctga cgacattgaa gctagccgaa tgaagcgagc agctgcaaag 120 catctaatagaacgctacta ccaccagtta actgagggct gtggaaatga agcctgcacg 180 aatgagttttgtgcttcctg tccaactttt cttcgtatgg ataataatgc agcagctatt 240 aaagccctcgagctttataa gattaatgca aaactctgtg atcctcatcc ctccaagaaa 300 ggagcaagctcagcttacct tgagaactcg aaaggtgccc ccaacaactc ctgctctgag 360 ataaaaatgaacaagaaagg cgctagaatt gattttaaag atgtgactta cttaacagaa 420 gagaaggtatatgaaattct tgaattatgt agagaaagag aggattattc ccctttaatc 480 cgtgttattggaagagtttt ttctagtgct gaggcattgg tacagagctt ccggaaagtt 540 aaacaacacaccaaggaaga actgaaatct cttcaagcaa aagatgaaga caaagatgaa 600 gatgaaaaggaaaaagctgc atgttctgct gctgctatgg aagaagactc agaagcatct 660 tcctcaaggataggtgatag ctcacaggga gacaacaatt tgcaaaaatt aggccctgat 720 gatgtgtctgtggatattga tgccattaga agggtctaca ccagattgct ctctaatgaa 780 aaaattgaaactgcctttct caatgcactt gtatatttgt cacctaacgt ggaatgtgac 840 ttgacgtatcacaatgtata ctctcgagat cctaattatc tgaatttgtt cattatcgta 900 atggagaatagaaatctcca cagtcctgaa tatctggaaa tggctttgcc attattttgc 960 aaagcgatgagcaagctacc ccttgcagcc caaggaaaac tgatcagact gtggtctaaa 1020 tacaatgcagaccagattcg gagaatgatg gagacatttc agcaacttat tacttataaa 1080 gtcataagcaatgaatttaa cagtcgaaat ctagtgaatg atgatgatgc cattgttgct 1140 gcttcgaagtgcttgaaaat ggtttactat gcaaatgtag tgggagggga agtggacaca 1200 aatcacaatgaagaagatga tgaagagccc atccctgagt ccagcgagct gacacttcag 1260 gaacttttgggagaagaaag aagaaacaag aaaggtcctc gagtggaccc cctggaaact 1320 gaacttggtgttaaaaccct ggattgtcga aaaccactta tcccttttga agagtttatt 1380 aatgaaccactgaatgaggt tctagaaatg gataaagatt atactttttt caaagtagaa 1440 acagagaacaaattctcttt tatgacatgt ccctttatat tgaatgctgt cacaaagaat 1500 ttgggattatattatgacaa tagaattcgc atgtacagtg aacgaagaat cactgttctc 1560 tacagcttagttcaaggaca gcagttgaat ccatatttga gactcaaagt tagacgtgac 1620 catatcatagatgatgcact tgtccggcta gagatgatcg ctatggaaaa tcctgcagac 1680 ttgaagaagcagttgtatgt ggaatttgaa ggagaacaag gagttgatga gggaggtgtt 1740 tccaaagaattttttcagct ggttgtggag gaaatcttca atccagatat tggtatgttc 1800 acatacgatgaatctacaaa attgttttgg tttaatccat cttcttttga aactgagggt 1860 cagtttactctgattggcat agtactgggt ctggctattt acaataactg tatactggat 1920 gtacattttcccatggttgt ctacaggaag ctaatgggga aaaaaggaac ttttcgtgac 1980 ttgggagactctcacccagt tctatatcag agtttaaaag atttattgga gtatgaaggg 2040 aatgtggaagatgacatgat gatcactttc cagatatcac agacagatct ttttggtaac 2100 ccaatgatgtatgatctaaa ggaaaatggt gataaaattc caattacaaa tgaaaacagg 2160 aaggaatttgtcaatcttta ttctgactac attctcaata aatcagtaga aaaacagttc 2220 aaggcttttcggagaggttt tcatatggtg accaatgaat ctcccttaaa gtacttattc 2280 agaccagaagaaattgaatt gcttatatgt ggaagccgga atctagattt ccaagcacta 2340 gaagaaactacagaatatga cggtggctat accagggact ctgttctgat tagggagttc 2400 tgggaaatcgttcattcatt tacagatgaa cagaaaagac tcttcttgca gtttacaacg 2460 ggcacagacagagcacctgt gggaggacta ggaaaattaa agatgattat agccaaaaat 2520 ggcccagacacagaaaggtt acctacatct catacttgct ttaatgtgct tttacttccg 2580 gaatactcaagcaaagaaaa acttaaagag agattgttga aggccatcac gtatgccaaa 2640 ggatttggcatgctgtaaaa caaaacaaaa caaaataaaa caaaaaaaaa aaaaaaaaaa 2700 aaaaaaaaaa2710 4 3997 DNA Homo sapiens 4 ctggccccaa ggtccgatcg cccaggggaggagcagcacc gggaccccgc gtcggctggg 60 cgccccacaa gggaagccag tcttaatatgatggaaacat ctctgaactt ctaaaagacc 120 aaggttggcg ttttagctct attaattttacttcgtcttg gccagaattc acaatgacaa 180 cagtgacagt gaccacagaa attcccccaagggataagat ggaagataat tctgccttgt 240 atgagtctac gtccgctcac attattgaagaaaccgagta tgtgaaaaag attcgaacta 300 ctctgcaaaa gatcaggacc cagatgtttaaagatgaaat aagacatgac agtacaaatc 360 acaaactaga tgcaaagcac tgtggaaaccttcaacaggg ctctgattct gaaatggatc 420 cttcttgttg cagtttggat ttgcttatgaaaaagataaa aggaaaagac ctacagctct 480 tagaaatgaa caaagagaat gaagtattgaaaatcaagct gcaagcctcc agagaagcag 540 gagcagcagc tctgagaaac gtggcccagagattatttga aaactaccaa acgcaatctg 600 aagaagtgag aaagaagcag gaggacagtaaacaattact ccaggttaac aagcttgaaa 660 aagaacagaa attgaaacaa catgttgaaaatctgaatca agttgctgaa aaacttgaag 720 aaaaacacag tcaaattaca gaattggagaaccttgtaca gagaatggaa aaggaaaaga 780 gaacactact agaaagaaaa ctgtctttggaaaacaagct actgcaactc aaatccagtg 840 ctacatatgg aaaaagttgc caggatcttcagagggagat ttccattctc caggagcaga 900 tctctcatct gcagtttgtg attcactcccaacatcagaa cctgcgcagt gtcatccagg 960 agatggaagg attaaaaaat aatttaaaagaacaagacaa aagaattgaa aatctcagag 1020 aaaaggttaa catacttgaa gcccagaataaagaactaaa aacccaggta gcactttcat 1080 ctgaaactcc taggacaaag gtatctaaggctgtctctac aagtgaattg aagaccgaag 1140 gtgtttcccc ttatttaatg ttgattaggttacggaaatg aactggctgg atgaagatct 1200 gatttagaaa gactgcgtga gtcttatttattctctgaaa cacagcccaa gtttcatgtt 1260 aaaatggcaa aatgccatta tttaaatggaacttattaca taccaatggc tttgcaagaa 1320 gatgacattt cagaagatca aacaaatctatatttaatgg atggactctt caaaacttac 1380 caaatagttg aagaaaccag gtgccttctcatgatggaag acagattctg ctttaaatta 1440 aaaaaaaaaa aaatctgaat cttgttttcagatttttttt tctactggga ttgttttaag 1500 attgtcaatt ctgacttttt tatagtggtttttaagagta taaatagaag ggagagtgta 1560 tatgtgtatg aatgaacata catttcctgcatatatatgt atgaagggca tgtatatgta 1620 tgaatgagca aacatatttg aaagttaacttttggatgat aggaaagatc gtacagtgac 1680 ataagttcat ctcctgatcc attgtttgtgggagaattat acttgactga attatgggca 1740 ggagaaagag cagattcctt ttagctaattccccaaccca tatgcccctc tgaagttgag 1800 aatcatggct gcctcaccac acatcagagaatgactgttc ttcttagttc tgggattaaa 1860 aattggtttc tagaggtaac ctgtacacacaaacgcacag ggatgcacat ggtttcctct 1920 gcctttgtga ctaattttct tcttgatagttattaatagt atctaaataa aatattgggg 1980 ggatagaaaa ataatgctgt tagctcatacttccatgaaa atgtatatat tataggctca 2040 aaggaataat gactgctgtc tgcagccagaaagaatctga atttatgaat tggaaagata 2100 tatatagtgt atttgtgaaa gtttgcttaaattctgatac atgccttctt tgtaggtgga 2160 gtttgtgatt gcagtgaata gaacaaattctgacttgcag aaatgcagac atacagtcag 2220 gaaagaacaa acttcaatta aatgtataatgagagacctt ggtcccccta aaggatgaat 2280 ttcctttagg cctttgatct tcctctctagtgtataactt taaatatttg ctcagaaaag 2340 atgctgactc tttcattatg gaatgtgaaatatcagtgtt gtctataaat atttgaaggt 2400 atataaaaat gagatgatgt aatgtatttataaatttatc caagtactgt aatccttgaa 2460 ttgttgtgta actgtgtgtg agttttatgcttcatggtat ttttggaaac atttttattg 2520 cttgcttatt ttgaaggtat atttatctgttaacatttag ggcatagtta ccttatacca 2580 gcaacaagtc taagcacttt acttgtattaatttatttta tcttccccaa ggccctcaga 2640 agcagattat tcctgtttta cagagaaagatactgagagt ggttgagtaa tttgcccagc 2700 tgctaactgt gaagcaaaaa tttgaaccttttgacttggc tattgatatt cattctactt 2760 gctcacatgg tggtctaaga aatttcccagctatagaaat ctctctattt ttgccacttt 2820 aatcaacaca tagcttcctg gatgactgcctgtgttattt tgtggatgac agtaagaaac 2880 aacaaatact gataaaatca atattttgctgaaatgagtt gatctttcac cagctggact 2940 accattgtga gaactcagtt cagacaaacttccctgctaa aaatctgttt atcatacatt 3000 tattatttat gactttatgt cacattgaagaatttcttca tgatacattt tcaggcacac 3060 ttgtaggaaa attaggatca tgagtcctgctttaagtatt tgcagtgtag taagagaatc 3120 catcttttac taggagacca gattccttttatacctcatt catcatgctg gattgtaata 3180 aatttcagat tttggaatgg gcttatttaactgacctaac aatcttgatg atttccatta 3240 gaataactta ttctaaggtc aaaagtggaaagacactgtt ggtttttatt ttgatttcac 3300 tatactcatt tttgaacatg gaaatacagtggtgaaacca cctatgcaaa aatgataaca 3360 gtgaggaaat tatgacagtg aaagagatctgacctaacta tctatcttgc ctcgaaactg 3420 cccttggtcg ttcctgagtg tgggccaagctaactttggg agaaatttac tttataggtt 3480 aaattataat agcccttccc aaaactaaacgattctcctg cctcagcctc ccgagtagct 3540 gtctttataa taccatcagc cttatcatttattcgtcatg tatggattgt ttcctatatc 3600 cactatcata aaattatcat ttgaaatatttttttatgaa aaaaaaaaca cttctcagtg 3660 aaaaaacaag attacaaggg ggaataatatttattcagct aaaatagtac ttcacaggaa 3720 atataggaaa agaaacacta gttcagttttattccaaata atgtacttct aattatactc 3780 ttgaatttat tggataagaa ggtctgaggtgggtctgaaa ttcatacatg aagtcaggaa 3840 aagaaaagaa acttagttct accttgattacatatgttgt tacaaattat cattataaaa 3900 tgtttaaaca attagtatag tatatcttttgaataattgc ttataatatg ccttaccata 3960 aagaaaattg atgctaaaaa aaaaaaaaaaaaaaaaa 3997 5 1592 DNA Homo sapiens 5 ctgctttgaa ggctgcacag aaaaccttacttgtttccac ctctgcagtt gataataatg 60 aagcacagaa aaaaaaacag gaggcattgaaacttcagca ggatgtaagg aaaaggaaac 120 aagaaatttt agaaaagcac attgaaacacagaagatgtt aatttcaaaa ctggagaaaa 180 acaaaacaat gaagtctgaa gataaagcagaaataatgaa aactttagag gttttgacaa 240 aaaatattac caagttgaaa gatgaggtcaaagctgcttc tcctggacgc tgtcttccaa 300 aaagtataaa aaccaagact cagatgcagaaggaattact tgacacagaa ctggatttat 360 ataagaagat gcaggctgga gaagaagtcactgaacttag gagaaagtat acagaattac 420 agctggaagc tgccaaacga gggattctttcatctggtcg gggcagagga attcattcaa 480 gaggtcgagg tgcagttcat ggccgaggcagggggcgagg gcgagggcga ggtgtgcctg 540 gtcatgctgt ggtggatcac cgtcccagggcattggagat ttctgcattt acggagagcg 600 atagagaaga tcttcttcct cattttgcgcaatatggtga aattgaagat tgtcagattg 660 atgattcctc acttcatgca gtaattacattcaagacaag agcagaagct gaagcagctg 720 cagttcatgg agctcgtttc aaagggcaagatctaaaact ggcatggaat aaaccagtaa 780 ctaatatttc agctgttgaa acagaagaagttgagcctga tgaagaagaa tttcaggaag 840 agtctttggt ggatgactca ttacttcaagatgatgatga agaagaagag gacaatgaat 900 ctcgttcttg gagaagatga tttgactgatcattgatctg catatgctag aactctacct 960 gtgtttcatt agtattatct aatgtacttttacatatttg taaaaacaat ttttggtaaa 1020 atgtgatgaa gatggatttc acaaatagacaaaaaagaag aaaactacct tctgatcttg 1080 tattttgaaa gattgatgtt tgcattttacttcagtaaac aattgctaaa gacatcacac 1140 tagaaacata tgcaatgttt ttattacatacttctactgg acatcacaga attctttggg 1200 ttctttgtaa tttaatgaat aggtctgaaaacttatgacc aatacttgtt ataacttaga 1260 ggactttgtt ttattccaaa taaggaatgaatttgcattt aaaatcttaa tgaatgtttt 1320 caaaactgaa tagataacat agtactctaactaaagtctc caagttatgt attataatat 1380 tacatagtag tatgcttagg ctttactatgtattagcctt ttgttggact gtgtatgtat 1440 tttaccatat gggttttaat gataatggtgtatgactgct ttacatgagt ccttatgcat 1500 ccagatgtta taataaagtg gaatggtctctttaaaaaaa aaaaaggaaa gaaaagagaa 1560 aagcaatgac aaaaaaaaaa aaaaaaaaaaaa 1592 6 2171 DNA Homo sapiens 6 aattcggcac gaggattctt gtgccaaaacagacataggc tcagaaaatt ctgaacaaat 60 agctaatttt cctagtggaa attttgctaaacatatttca aaaacaaatg aaacagaaca 120 gaaagtaaca caaatattgg tggaattaaggtcatctaca tttccagaat cagctaatga 180 aaagacttat tcagaaagcc cctatgatacagactgcacc aagaaattta tttcaaaaat 240 aaagagcgtt tcagcatcag aggatttgttggaagaaata gaatctgagc tcttatctac 300 ggagtttgca gaacatcaag taccaaatggaatgaataag ggagaacatg cattagttct 360 gtttgaaaag tgtgtgcaag ataaatatttgcagcaggaa catatcataa aaaagttaat 420 taaagaaaat aagaagcatc aggagctcttcgtagacatt tgttcagaaa aagacaattt 480 aagagaagaa ctaaagaaaa gaacagaaactgagaagcag catatgaaca caattaaaca 540 gttagaatca agaatagaag aacttaataaagaagttaaa gcttccagag ataaactaat 600 agctcaagac gttacagcta aaaatgcagttcagcagtta cacaaagaga tggcccaacg 660 gatggaacag gccaacaaga aatgtgaagaggcacgccaa gaaaaagaag caatggtaat 720 gaaatatgta agaggtgaga aggaatctttagatcttcga aaggaaaaag agacacttga 780 gaaaaaactt agagatgcaa ataaggaacttgagaaaaac actaacaaaa ttaagcagct 840 ttctcaggag aaaggacggt tgcaccagctgtatgaaact aaggaaggcg aaacgactag 900 actcatcaga gaaatagaca aattaaaggaagacattaac tctcacgtca tcaaagtaaa 960 gtgggcacaa aacaaattaa aagctgaaatggattcacac aaggaaacca aagataaact 1020 caaagaaaca acaacaaaat taacacaagcaaaggaagaa gcagatcaga tacgaaaaaa 1080 ctgtcaggat atgataaaaa catatcaggagtcagaagaa attaaatcaa atgagcttga 1140 tgcaaagctt agagtcacaa aaggagaacttgaaaaacaa atgcaagaaa aatctgacca 1200 gctagagatg catcatgcca aaataaaggaactagaagat ctgaagagaa catttaagga 1260 gggtatggat gagttaagaa cactgagaacaaaggtgaaa tgtctagaag atgaacgatt 1320 aagaacagaa gatgaattat caaaatataaggaaattatt aatcgccaaa aagctgaaat 1380 tcagaattta ttggacaagg tgaaaactgcagatcagcta caggagcagc ttcaaagagg 1440 taagcaagaa attgaaaatt tgaaagaagaagtggaaagt cttaattctt tgattaatga 1500 cctacaaaaa gacatcgaag gcagtaggaaaagagaatct gagctgctgc tgtttacaga 1560 aaggctcact agtaagaatg cacagcttcagtctgaatcc aattctttgc agtcacaatt 1620 tgataaagtt tcctgtagtg aaagtcagttacaaagccag tgtgaacaaa tgaaacagac 1680 aaatattaat ttggaaagta ggttgttgaaagaggaagaa ctgcgaaaag aggaagtcca 1740 aactctgcaa gctgaactcg cttgtagacaaacagaagtt aaagcattga gtacccaggt 1800 agaagaatta aaagatgagt tagtaactcagagacgtaaa catgcctcta gtatcaagga 1860 tctcaccaaa caacttcagc aagcacgaagaaaattagat caggttgaga gtggaagcta 1920 tgacaaagaa gtcagcagca tgggaagtcgttctagttca tcagggtccc tgaatgctcg 1980 aagcagtgca gaagatcgat ctccagaaaatactgggtcc tcagtagctg tggataactt 2040 tccacaagta gataaggcca tgttgattgagagaatagtt aggctgcaaa aagcacatgc 2100 ccggaaaaat gaaaagatag aatttatggaggaccacatc aaacaactgg tggaaaaaaa 2160 aaaaaaaaaa a 2171 7 3513 DNA Homosapiens 7 ctcgaaatta accctcacta aagggaacaa aagctggagc tccaccgcggtggcggccgc 60 tctagaacta gtggatcccc cgggctgcag gaattcggca cgaggtgatgctgctgctgc 120 tgctgctgct gccgccgccg cctctattgc tgatactcta gtggggctggaagggtggtt 180 cctattcgca ccatcgccaa ccagagacag agggaaaaaa aaaaccggcagccactgctg 240 atgttgggtt cggaggctgc atccgactcg gtcacaagga aaatggattcagtttgcatc 300 tctccctcct ttaaacagct tctccgggtc tcagcatggg cttccagggcagcgattgag 360 gagaccttac caaggagcac cacacagtag atgctgagac atcgtactccaggataagaa 420 acagtaacat ggcagcacct gcttgaaaga aattaaaaac caacagactccatttagaaa 480 ggaacaatgt ccaagaaagg gcgaaataag ggcgagaagc ccgaggcactcattgttgcc 540 cttcaagctg ccaatgaaga cctcaggacc aagctcacag acattcagatagagctgcat 600 caagagaagt ccaaggtatc aaagcttgaa agagagaaga ctcaagaagcgaagaggatt 660 cgtgagctgg agcagcgcaa gcacacggtg ctggtgacag aactcaaagccaagctccat 720 gaggagaaga tgaaggagct gcaggctgtg agggagaacc ttatcaagcagcacgagcag 780 gaaatgtcaa ggacggtgaa ggtacgtgat ggagagatcc agaggctcaagtctgctctc 840 tgtgctctcc gcgacggcag cagtgacaaa gtaaggacag cgctcaccattgaggcccgg 900 gaggaggccc ggaaactgtt tgacacagag cgccttaagc tcttacaggaaattgcggac 960 ctgaaaacgg ccaagaagca ggtggacgag gctctgagca atatgatccaagcagataaa 1020 atcaaggctg gggaccttcg gagtgagcat cagtcccacc aagaagccatctcgaagatc 1080 aagtgggagt cggagcggga tattcggagg ctgatggatg aaatcaaagccaaggacagg 1140 atcatctttt ccctggaaaa ggaactggag acccagacag gctatgtacagaaactccaa 1200 cttcagaagg aggctttgga cgaacaactc tttctggtca aggaggctgagtgcaacatg 1260 agcagcccaa aacgagaaat tccaggaagg gcaggtgatg gttccgaacactgcagcagt 1320 cctgatttgc gaagaaatca aaagagaata gctgaattga atgccactataagaaaatta 1380 gaagacagga ataccttgct tggagatgaa cgaaatgaac tgttaaaacgtgtgcgggaa 1440 accgaaaagc aatgtaaacc tctcctggaa aggaacaagt gcctcgccaagagaaacgat 1500 gaactgatgg tgtccttgca gcgcatggaa gaaaaactaa aagccgttaccaaggaaaat 1560 tcagaaatga gagaaaaaat aacatcccat ccacccctga agaaattaaaatctctgaat 1620 gacctcgacc aagctaatga agaacaagaa acagagtttc taaaacttcaggtcattgag 1680 caacagaaca ttattgatga gctcacaagg gaccgagaaa agctcatccgtagaagaaag 1740 catagaagaa gttccaagcc aattaagagg cctgttttgg acccgtttattggctatgat 1800 gaggactcta tggattcaga gacatcatcc atggcctcat ttagaacagacagaacacca 1860 gctactcctg atgatgactt ggatgaaagt ttagcagctg aagaatctgaactaagattt 1920 cgacaattaa caaaagaata tcaggccctc caaagagcat atgccctcctacaggagcag 1980 acgggaggca tcatcgacgc tgaacgagaa gccaaggctc aagaacagctccaagcagag 2040 gtgctaaggt ataaagccaa aattgaagac ctggaagcga ctctggctcagaaagggcag 2100 gattcacact gggtagaaga taaacaactt ttcattaaga gaaaccaggagcttttagaa 2160 aagatagaaa aacaggaggc agaaaatcac cggttacaac aagaactacaggacgccaga 2220 gaccagaatg agctgctgga gtttcgaaac ctagagctag aagagagagagagacgatcc 2280 cctccattta atctccaaat tcacccattc tcagatggtg tgagtgctctacagatctac 2340 tgtatgaaag aaggtgttaa ggatgtgaac atccctgatc tcataaagcagcttgatatc 2400 ttgggtgata atgggaattt aagaaatgaa gaacaagtgg ccataattcaggccagcact 2460 gtgctgtccc tggcagagaa gtggatccag cagattgaag gagctgaggctgccctacac 2520 cagaaaatga tggaattgga aagtgacatg gaacagttct gcaaaataaaaggctatctg 2580 gaggaagaac tagactacag aaaacaagct cttgaccaag catatatgagaatccaggaa 2640 ctagaagcta ctttgtacaa tgctctacag caagaaactg ttatcaagtttggtgaatta 2700 ttaagtgaaa aacagcaaga ggagctgagg acggcagtag aaaagttacggcggcaaatg 2760 ctgaggaaga gcagagagta tgactgtcag attcttcagg agagaatggagctcttacag 2820 caagcccatc agagaattcg tgacttagaa gataaaacag acatccagaaaagacaaata 2880 aaagacttag aagaaaagag taaccgaaaa catggataag atcccaggaagacaagtgct 2940 tctaaacctt caaagatggc aaaattgttt acaccagtga gagggagatcaaaagctaag 3000 aactaccctg tagccaggac tacaactgtg tattttaaag ccattattcaaggtttctta 3060 cttgacagtt cctacacaac cctgttgaaa atctacaata tatgctgcatttaatgaaac 3120 atgtatatgt caaatcagaa gagaagaact ataaacatat attgtgtaaagaaaaagttc 3180 agcaatggaa ctagtttctg cagatcaagc aaagatgtgt cttgggcatggaaccaaagt 3240 tacaatgaaa tattcaaccc ctgctgtgca ggggggtcat tttaatgtaacaccacaccc 3300 catggaaaca ctagtcctga taataaacat cattttaaaa gatcaaaacaaacaaacaaa 3360 aaaaacaagg gtgggtgggg agtgaagcac gaggaatacc tatgaagagctatttacaat 3420 aaaatgtttc atttgaaaag tcaaaaaaaa aaaaaaaaaa actcgagggggggcccggta 3480 cccaattcgc cctatagtga gtcgtattac aat 3513 8 1465 DNAHomo sapiens 8 aattcggcac gaggcgcggg ccgctgtgag gcgcggcggc gagcgacgggcgcggggccg 60 cggagcagcg agcgagcgag cgagcgcgag gccggagccc cggccaggcccggccgaccc 120 gccgagcccg cgatgcgccc cggggccgcc ccccggcgca gctgacgccccgcggccccg 180 cgaagacccc ggccggccgg tcccggagga agcggccgcc gccgccgccgcccagcccag 240 cgcccgcgcc gcccgggcac catggcgggg aaggcggccg ccccgggcaccgcggtgctg 300 ctggtcacgg ccaacgtggg ctcgctcttc gacgacccag aaaacctgcagaagaactgg 360 cttcgggaat tttaccaggt cgtgcacaca cacaggccgc acttcatggccttgcactgt 420 caggagtttg gagggaagaa ctacgaggcc tccatgtccc acgtggacaagttcgtcaaa 480 gaactattgt cgagtgatgc gatgaaagaa tataacaggg ctcgagtctacctggatgaa 540 aactacaaat cccaggagca cttcacggca ctaggaagct tttattttcttcatgagtcc 600 ttaaaaaaca tctaccagtt tgactttaaa gctaagaagt atagaaaggtcgctggcaaa 660 gagatctact cggatacctt agagagcacg cccatgctgg agaaggagaagtttccgcag 720 gactacttcc ccgagtgcaa atggtcaaga aaaggcttca tccggacgaggtggtgcatt 780 gcagactgtg cctttgactt ggtgaatatc catcttttcc atgatgcttccaatctggtc 840 gcctgggaaa caagcccttc cgtgtactcg ggaatccggc acaaggcactgggctacgtg 900 ctggacagaa tcattgatca gcgattcgag aaggtttcct actttgtatttggtgatttc 960 aacttccggc tggattccaa gtccgtcgtg gagacgctct gcacaaaagccaccatgcag 1020 acggtccggg ccgccgacac caatgaagtg gtgaagctca tatttcgtgagtcggacaac 1080 gaccggaagg ttatgctcca gttagaaaag aaactcttcg actacttcaaccaggaggtt 1140 ttccgagaca acaacggcac cgcgctcttg gagtttgaca aggagttgtctgtctttaag 1200 gacagactgt atgaactgga catctcgttc cctcccagct acccgtacagtgaggacgcc 1260 cgccagggtg agcagtacat gaacacccgg tgcccagcct ggtgtgaccgcatcctcatg 1320 tccccgtctg ccaaggagct ggtgctgcgg gtgagtgtgt gctgccccagccctgggcac 1380 agagggatgt ggagcgctgg gtctggtctg gcccagccct ggtgacagggccccaggggt 1440 gggggaaaaa aaaaaaaaaa aaaaa 1465 9 1681 DNA Homo sapiens9 gagggttaga tcgagcaacc ctctaaaagc agtttagagt ggtaaaaaaa aaaaaaacac 60accaaacgct cgcagccaca aaagggatga aatttcttct ggacatcctc ctgcttctcc 120cgttactgat cgtctgctcc ctagagtcct tcgtgaagct ttttattcct aagaggagaa 180aatcagtcac cggcgaaatc gtgctgatta caggagctgg gcatggaatt gggagactga 240ctgcctatga atttgctaaa cttaaaagca agctggttct ctgggatata aataagcatg 300gactggagga aacagctgcc aaatgcaagg gactgggtgc caaggttcat acctttgtgg 360tagactgcag caaccgagaa gatatttaca gctctgcaaa gaaggtgaag gcagaaattg 420gagatgttag tattttagta aataatgctg gtgtagtcta tacatcagat ttgtttgcta 480cacaagatcc tcagattgaa aagacttttg aagttaatgt acttgcacat ttctggacta 540caaaggcatt tcttcctgca atgacgaaga ataaccatgg ccatattgtc actgtggctt 600cggcagctgg acatgtttcg gtccccttct tactggctta ctgttcaagc aagtttgctg 660ctgttggatt tcataaaact ttgacagatg aactggctgc cttacaaata actggagtca 720aaacaacatg tctgtgtcct aatttcgtaa acactggctt catcaaaaat ccaagtacaa 780gtttgggacc cactctggaa cctgaggaag tggtaaacag gctgatgcat gggattctga 840ctgagcagaa gatgattttt attccatctt ctatagcttt tttaacaaca ttggaaagga 900tccttcctga gcgtttcctg gcagttttaa aacgaaaaat cagtgttaag tttgatgcag 960ttattggata taaaatgaaa gcgcaataag cacctagttt tctgaaaact gatttaccag 1020gtttaggttg atgtcatcta atagtgccag aattttaatg tttgaacttc tgttttttct 1080aattatcccc atttcttcaa tatcattttt gaggctttgg cagtcttcat ttactaccac 1140ttgttcttta gccaaaagct gattacatat gatataaaca gagaaatacc tttagaggtg 1200actttaagga aaatgaagaa aaagaaccaa aatgacttta ttaaaataat ttccaagatt 1260atttgtggct cacctgaagg ctttgcaaaa tttgtaccat aaccgtttat ttaacatata 1320tttttatttt tgattgcact taaattttgt ataatttgtg tttctttttc tgttctacat 1380aaaatcagaa acttcaagct ctctaaataa aatgaaggac tatatctagt ggtatttcac 1440aatgaatatc atgaactctc aatgggtagg tttcatccta cccattgcca ctctgtttcc 1500tgagagatac ctcacattcc aatgccaaac atttctgcac agggaagcta gaggtggata 1560cacgtgttgc aagtataaaa gcatcactgg gatttaagga gaattgagag aatgtaccca 1620caaatggcag caataataaa tggatcacac ttaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1680 a1681 10 1980 DNA Homo sapiens 10 aattcggcac gaggttcact ctttgcaataaatcttgctg ctgctcactc tttgggtcca 60 cactgccttt atgagctgta acactcactgggaatgtctg cagcttcact cctgaagcca 120 gcgagaccac gaacccacca ggaggaacaaacaactccag acgcgcagcc ttaagagctg 180 taacactcac cgcgaaggtc tgcagcttcactcctgagcc agccagacca cgaacccacc 240 agaaggaaga aactccaaac acatccgaacatcagaagga gcaaactcct gacacgccac 300 ctttaagaac cgtgacactc aacgctagggtccgcggctt cattcttgaa gtcagtgaga 360 ccaagaaccc accaattccg gacacgctaattgttgtaga tcatcacttc aaggtgccca 420 tatctttcta gtggaaaaat tattctggcctccgctgcat acaaatcagg caaccagaat 480 tctacatata taaggcaaag taacatcctagacatggctt tagagatcca catgtcagac 540 cccatgtgcc tcatcgagaa ctttaatgagcagctgaagg ttaatcagga agctttggag 600 atcctgtctg ccattacgca acctgtagttgtggtagcga ttgtgggcct ctatcgcact 660 ggcaaatcct acctgatgaa caagctggctgggaagaaca agggcttctc tgtgcatcta 720 cggtgcagtc tcacaccaag ggaatttggatatggtgtgt gcctcatccc aactggccaa 780 atcacacatt agttctgctt gacaccgagggcctgggaga tgtagagaag gctgacaaca 840 agaatgatat ccagatcttt gcactggcactcttagtgag cagcaccttt gtgtacaata 900 ctgtgaacaa aattgatcag ggtgctatcgacctactgca caatgtgaca gaactgacag 960 atctgctcaa ggcaagaaac tcacccgaccttgacagggt tgaagatcct gctgactctg 1020 cgagcttctt cccagactta gtgtggactctgagagattt ctgcttaggc ctggaaatag 1080 atgggcaact tgtcacacca gatgaatacctggagaattc cctaaggcca aagcaaggta 1140 gtgatcaaag agttcaaaat ttcaatttgccccgtctgtg tatacagaag ttctttccaa 1200 aaaagaaatg ctttatcttt gacttacctgctcaccaaaa aaagcttgcc caacttgaaa 1260 cactgcctga tgatgagcta gagcctgaatttgtgcaaca agtgacagaa ttctgttcct 1320 acatctttag ccattctatg accaagactcttccaggtgg catcatggtc aatggatctc 1380 gtctaaagaa cctggtgctg acctatgtcaatgccatcag cagtggggat ctgccttgca 1440 tagagaatgc agtcctggcc ttggctcagagagagaactc agctgcagtg caaaaggcca 1500 ttgcccacta tgaccagcaa atgggccagaaagtgcagct gcccatggaa accctccagg 1560 agctgctgga cctgcacagg accagtgagagggaggccat tgaagtcttc atgaaaaact 1620 ctttcaagga tgtagaccaa agtttccagaaagaattgga gactctacta gatgcaaaac 1680 agaatgacat ttgtaaacgg aacctggaagcatcctcgga ttattgctcg gctttactta 1740 aggatatttt tggtcctcta gaagaagcagtgaagcaggg aatttattct aagccaggag 1800 gccataatct cttcattcag aaaacagaagaactgaaggc aaagtactat cgggagcctc 1860 ggaaaggaat acaggctgaa gaagttctgcagaaatattt aaagtccaag gagtctgtga 1920 gtcatgcaat attacagact gaccaggctctcacagagac ggaaaaaaaa aaaaaaaaaa 1980 11 1494 DNA Homo sapiens 11aattcggcac gagggtggaa atttgagacc agcaagtact atgtgactat cattgatgcc 60ccaggacaca gagactttat caaaaacatg attacaggga catctcaggc tgactgtgct 120gtcctgattg ttgctgctgg tgttggtgaa tttgaagctg gtatctccaa gaatgggcag 180acccgagagc atgcccttct ggcttacaca ctgggtgtga aacaactaat tgtcggtgtt 240aacaaaatgg attccactga gccaccctac agccagaaga gatatgagga aattgttaag 300gaagtcagca cttacattaa gaaaattggc tacaaccccg acacagtagc atttgtgcca 360atttctggtt ggaatggtga caacatgctg gagccaagtg ctaacatgcc ttggttcaag 420ggatggaaag tcacccgtaa ggatggcaat gccagtggaa ccacgctgct tgaggctctg 480gactgcatcc taccaccaac tcgtccaact gacaagccct tgcgcctgcc tctccaggat 540gtctacaaaa ttggtggtat tggtactgtt cctgttggcc gagtggagac tggtgttctc 600aaacccggta tggtggtcac ctttgctcca gtcaacgtta caacggaagt aaaatctgtc 660gaaatgcacc atgaagcttt gagtgaagct cttcctgggg acaatgtggg cttcaatgtc 720aagaatgtgt ctgtcaagga tgttcgtcgt ggcaacgttg ctggtgacag caaaaatgac 780ccaccaatgg aagcagctgg cttcactgct caggtgatta tcctgaacca tccaggccaa 840ataagcgccg gctatgcccc tgtattggat tgccacacgg ctcacattgc atgcaagttt 900gctgagctga aggaaaagat tgatcgccgt tctggtaaaa agctggaaga tggccctaaa 960ttcttgaagt ctggtgatgc tgccattgtt gatatggttc ctggcaagcc catgtgtgtt 1020gagagcttct cagactatcc acctttgggt cgctttgctg ttcgtgatat gagacagaca 1080gttgcggtgg gtgtcatcaa agcagtggac aagaaggctg ctggagctgg caaggtcacc 1140aagtctgccc agaaagctca gaaggctaaa tgaatattat ccctaatacc tgccacccca 1200ctcttaatca gtggtggaag aacggtctca gaactgtttg tttcaattgg ccatttaagt 1260ttagtagtaa aagactggtt aatgataaca atgcatcgta aaaccttcag aaggaaagga 1320gaatgttttg tggaccactt tggttttctt ttttgcgtgt ggcagtttta agttattagt 1380ttttaaaatc agtacttttt aatggaaaca acttgaccaa aaatttgtca cagaattttg 1440agacccatta aaaaagttaa atgagaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1494 12 2564DNA Homo sapiens 12 ccacgcgctc cgggccgctc aggctgagcg atttcccgccttttctgagg ttctgaggcg 60 ggagccattg gttctttctg ttgccctcat agaccgtatgtagcagttcg cgtgggcaca 120 gaacccacgg tttcccgcta gttcttcaaa gtagatatttacaaccgtaa cagagaaaat 180 ggaaaagcaa aagccctttg cattgttcgt accaccgagatcaagcagca gtcaggtgtc 240 tgcggtgaaa cctcagaccc tgggaggcga ttccactttcttcaagagtt tcaacaaatg 300 tactgaagat gattttgagt ttccatttgc aaagactaatctctccaaaa atggggaaaa 360 cattgattca gatcctgctt tacaaaaagt taatttcttgcccgtgcttg agcaggttgg 420 taattctgac tgtcactatc aggaaggact aaaagactctgatttggaga attcagaggg 480 attgagcaga gtgtattcaa aactgtataa ggaggctgaaaagataaaaa aatggaaagt 540 aagtacagaa gctgaactga gacagaaaga aagtaagttgcaagaaaaca gaaagataat 600 tgaagcacag cgaaaagcca ttcaggaact gcaatttggaaatgaaaaag taagtttgaa 660 attagaagaa ggaatacaag aaaataaaga tttaataaaagagaataatg ccacaaggca 720 tttatgtaat ctactcaaag aaacctgtgc tagatctgcagaaaagacaa agaaatatga 780 atatgaacgg gaagaaacca ggcaagttta tatggatctaaataataaca ttgagaaaat 840 gataacagct tttgaggaac ttcgtgtgca agctgagaattccagactgg aaatgcattt 900 taagttaaag gaagattatg aaaaaatcca acaccttgaacaagaataca agaaggaaat 960 aaatgacaag gaaaagcagg tatcactact attgatccaaatcactgaga aagaaaataa 1020 aatgaaagat ttaacatttc tgctagagga atccagagataaagttaatc aattagagga 1080 aaagacaaaa ttacagagtg aaaacttaaa acaatcaattgagaaacagc atcatttgac 1140 taaagaacta gaagatatta aagtgtcatt acaaagaagtgtgagtactc aaaaggcttt 1200 agaggaagat ttacagatag caacaaaaac aatttgtcagctaactgaag aaaaagaaac 1260 tcaaatggaa gaatctaata aagctagagc tgctcattcgtttgtggtta ctgaatttga 1320 aactactgtc tgcagcttgg aagaattatt gagaacagaacagcaaagat tggaaaaaaa 1380 tgaagatcaa ttgaaaatac ttaccatgga gcttcaaaagaaatcaagtg agctggaaga 1440 gatgactaag cttacaaata acaaagaagt agaacttgaagaattgaaaa aagtcttggg 1500 agaaaaggaa acacttttat atgaaaataa acaatttgagaagattgctg aagaattaaa 1560 aggaacagaa caagaactaa ttggtcttct ccaagccagagagaaagaag tacatgattt 1620 ggaaatacag ttaactgcca ttaccacaag tgaacagtattattcaaaag aggttaaaga 1680 tctaaaaact gagcttgaaa acgagaagct taagaatactgaattaactt cacactgcaa 1740 caagctttca ctagaaaaca aagagctcac acaggaaacaagtgatatga ccctagaact 1800 caagaatcag caagaagata ttaataataa caaaaagcaagaagaaagga tgttgaaaca 1860 aatagaaaat cttcaagaaa cagaaaccca attaagaaatgaactagaat atgtgagaga 1920 agagctaaaa cagaaaagag atgaagttaa atgtaaattggacaagagtg aagaaaattg 1980 taacaattta aggaaacaag ttgaaaataa aaacaagtatattgaagaac ttcagcagga 2040 gaataaggcc ttgaaaaaaa aaggtacagc agaaagcaagcaactgaatg tttatgagat 2100 aaaggtcaat aaattagagt tagaactaga aagtgccaaacagaaatttg gagaaatcac 2160 agacacctat cagaaagaaa ttgaggacaa aaagatatcagaagaaaatc ttttggaaga 2220 ggttgagaaa gcaaaagtaa tagctgatga agcagtaaaattacagaaag aaattgataa 2280 gcgatgtcaa cataaaatag ctgaaatggt agcacttatggaaaaacata agcaccaata 2340 tgataagatc attgaagaaa gagactcaga attaggactttataagagca aagaacaaga 2400 acagtcatca ctgagagcat ctttggagat tgaactatccaatctcaaag ctgaactttt 2460 gtctgttaag aagcaacttg aaatagaaag agaagagaaggaaaaactca aaagagaggc 2520 aaaagaaaac acagctactc ttaaagaaaa aaaaaaaaaaaaaa 2564 13 2317 DNA Homo sapiens 13 ctaccaacaa gcattttatt cgtctggctgagatggaaca gacagtagca gaacaagatg 60 actctctttc ctcactcttg gtcaaactaaagaaagtatc acaagatttg gagagacaaa 120 gagaaatcac tgaattaaaa gtaaaagaatttgaaaatat caaattacag cttcaagaaa 180 accatgaaga tgaagtgaaa aaagtaaaagcggaagtaga ggatttaaag tatcttctgg 240 accagtcaca aaaggagtca cagtgtttaaaatctgaact tcaggctcaa aaagaagcaa 300 attcaagagc tccaacaact acaatgagaaatctagtaga acggctaaag agccaattag 360 ccttgaagga gaaacaacag aaagcacttagtcgggcact tttagaactc cgggcagaaa 420 tgacagcagc tgctgaagaa cgtattatttctgcaacttc tcaaaaagag gcccatctca 480 atgttcaaca aatcgttgat cgacatactagagagctaaa gacacaagtt gaagatttaa 540 atgaaaatct tttaaaattg aaagaagcacttaaaacaag taaaaacaga gaaaactcac 600 taactgataa tttgaatgac ttaaataatgaactgcaaaa gaaacaaaaa gcctataata 660 aaatacttag agagaaagag gaaattgatcaagagaatga tgaactgaaa aggcaaatta 720 aaagactaac cagtggatta cagggcaaacccctgacaga taataaacaa agtctaattg 780 aagaactcca aaggaaagtt aaaaaactagagaaccaatt agagggaaag gtggaggaag 840 tagacctaaa acctatgaaa gaaaagaatgctaaagaaga attaattagg tgggaagaag 900 gtaaaaagtg gcaagccaaa atagaaggaattcgaaacaa gttaaaagag aaagaggggg 960 aagtctttac tttaacaaag cagttgaatactttgaagga tctttttgcc aaagccgata 1020 aagagaaact tactttgcag aggaaactaaaaacaactgg catgactgtt gatcaggttt 1080 tgggaatacg agctttggag tcagaaaaagaattggaaga attaaaaaag agaaatcttg 1140 acttagaaaa tgatatattg tatatgagggcccaccaagc tcttcctcga gattctgttg 1200 tagaagattt acatttacaa aatagatacctccaagaaaa acttcatgct ttagaaaaac 1260 agttttcaaa ggatacatat tctaagccttcaatttcagg aatagagtca gatgatcatt 1320 gtcagagaga acaggagctt cagaaggaaaacttgaagtt gtcatctgaa aatattgaac 1380 tgaaatttca gcttgaacaa gcaaataaagatttgccaag attaaagaat caagtcagag 1440 atttgaagga aatgtgtgaa tttcttaagaaagaaaaagc agaagttcag cggaaacttg 1500 gccatgttag agggtctggt agaagtggaaagacaatccc agaactggaa aaaaccattg 1560 gtttaatgaa aaaagtagtt gaaaaagtccagagagaaaa tgaacagttg aaaaaagcat 1620 caggaatatt gactagtgaa aaaatggctaatattgagca ggaaaatgaa aaattgaagg 1680 ctgaattaga aaaacttaaa gctcatcttgggcatcagtt gagcatgcac tatgaatcca 1740 agaccaaagg cacagaaaaa attattgctgaaaatgaaag gcttcgtaaa gaacttaaaa 1800 aagaaactga tgctgcagag aaattacggatagcaaagaa taatttagag atattaaatg 1860 agaagatgac agttcaacta gaagagactggtaagagatt gcagtttgca gaaagcagag 1920 gtccacagct tgaaggtgct gacagtaagagctggaaatc cattgtggtt acaagaatgt 1980 atgaaaccaa gttaaaagaa ttggaaactgatattgccaa aaaaaatcaa agcattactg 2040 accttaaaca gcttgtaaaa gaagcaacagagagagaaca aaaagttaac aaatacaatg 2100 aagaccttga acaacagatt aagattcttaaacatgttcc tgaaggtgct gagacagagc 2160 aaggccttaa acgggagctt caagttcttagattagctaa tcatcagctg gataaagaga 2220 aagcagaatt aatccatcag atagaagctaacaaggacca aagtggagct gaaagcacca 2280 tacctgatgc tgatcaacta aaaaaaaaaaaaaaaaa 2317 14 2234 DNA Homo sapiens 14 aggatgagga tgggacagaagaggataaca gtcgtgttga acctgttgga catgctgaca 60 cgggtttgga gcatatacccaacttttctc tggatgatat ggtaaagctc gtagaagtcc 120 ccaacgatgg agggcctctgggaatccatg tagtgccttt cagtgctcga ggcggcagaa 180 ccctggggtt attagtaaaacgattggaga aaggtggtaa agctgaacat ctgaacatga 240 aaatcttttt cgtgagaatgattgcattgt caggattaat gatggcgacc ttcgaaatag 300 aagatttgaa caagcacaacatatgtttcg ccaagccatg cgtacaccca tcatttggtt 360 ccatgtggtt cctgcagcaaataaagagca gtatgaacaa ctatcccaaa gtgagaagaa 420 caattactat tcaagccgttttagccctga cagccagtat attgacaaca ggagtgtgaa 480 cagtgcaggg cttcacacggtgcagagagc accccgactg aaccacccgc ctgagcagat 540 agactctcac tcaagactacctcatagcgc acacccctcg ggaaaaccac catccgctcc 600 agcctcggca cctcagaatgtatttagtac gactgtaagc agtggttata acaccaaaaa 660 aataggcaag aggcttaatatccagcttaa gaaaggtaca gaaggtttgg aattcagcat 720 cacttccaga gatgtaacaataggtggctc agctccaatc tatgtgaaaa acattctccc 780 ccggggggcg gccattcaggatggccgact taaggcagga gacagactta tagaggtaaa 840 tggagtagat ttagtgggcaaatcccaaga ggaagttgtt tcgctgttga gaagcaccaa 900 gatggaagga actgtgagccttctggtctt tcgccaggaa gacgccttcc acccaaggga 960 actgaatgca gagccaagccagatgcagat tccaaaagaa acgaaagcag aagatgagga 1020 tattgttctt acacctgatggcaccaggga atttctgaca tttgaagtcc cacttaatga 1080 ttcaggatct gcaggccttggtgtcagtgt caaaggtaac cggtcaaaag agaaccacgc 1140 agatttggga atctttgtcaagtccattat taatggagga gcagcatcta aagatggaag 1200 gcttcgggtg aatgatcaactgatagcagt aaatggagaa tccctgttgg gcaagacaaa 1260 ccaagatgcc atggaaaccctaagaaggtc tatgtctact gaaggcaata aacgaggaat 1320 gatccagctt attgttgcaaggagaataag caagtgcaat gagctgaagt cacctgggag 1380 cccccctgga cctgagctgcccattgaaac agcgttggat gatagagaac gaagaatttc 1440 ccattccctc tacagtgggattgaggggct tgatgaatcg cccagcagaa atgctgccct 1500 cagtaggata atgggtgagtcaggtaaata ccagctgtcc cctacagtga atatgcccca 1560 agatgacact gtcattatagaagatgacag gttgccagtg cttcctccac atctctctga 1620 ccagtcctct tccagctcccatgatgatgt ggggtttgtg acggcagatg ctggtacttg 1680 ggccaaggct gcaatcagtgattcagccga ctgctctttg agtccagatg ttgatccagt 1740 tcttgctttt caacgagaaggatttggacg tcagatagct gacgagacta aactcaatac 1800 agtggatgac cagaaagcaggttctcccag cagagatgtg ggtccttccc tgggtctgaa 1860 gaagtcaagc tcgttggagagtctgcagac cgcagttgcc gaggtgactt tgaatgggga 1920 tattcctttc catcgtccacggccgcggat aatcagaggc aggggatgca atgagagctt 1980 cagagctgcc atcgacaaatcttatgataa acccgcggta gatgatgatg atgaaggcat 2040 ggagaccttg gaagaagacacagaagaaag ttcaagatca gggagagagt ctgtatccac 2100 agccagtgat cagccttcccactctctgga gagacaaatg aatggaaacc aagagaaagg 2160 tgataagact gatagaaaaaaaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2220 aaaaaaaaaa aaaa 2234 152620 DNA Homo sapiens 15 atcaaatgct gctcgatccc accaacccca gcgccggcactgccaagata gacaagcagg 60 agaaggtcaa gctcaacttt gacatgacgg catcccccaagatcctgatg agcaagcctg 120 tgctgagtgg gggcacaggc cgccggattt ccttgtcggatatgccgcgc tcccccatga 180 gcacaaactc ttctgtgcac acgggctccg acgtggagcaggatgctgag aagaaggcca 240 cgtcgagcca cttcagtgcg agcgaggagt ccatggacttcctggataag agcacagctt 300 caccagcctc caccaagacg ggacaagcag ggagtttatccggcagccca aagcccttct 360 ctcctcaact gtcagctcct atcacgacga aaacggacaaaacctccacc accggcagca 420 tcctgaatct taacctggat cgaagcaaag ctgagatggatttgaaggag ctgagcgagt 480 cggtccagca acagtccacc cctgttcctc tcatctctcccaagcgccag attcgtagca 540 ggttccagct gaatcttgac aagaccatag agagttgcaaagcacaatta ggcataaatg 600 aaatctcgga agatgtctat acggccgtag agcacagcgattcggaggat tctgagaagt 660 cagatagtag cgatagtgag tatatcagtg atgatgagcagaagtctaag aacgagccag 720 aagacacaga ggacaaagaa ggttgtcaga tggacaaagagccatctgct gttaaaaaaa 780 agcccaagcc tacaaaccca gtggagatta aagaggagctgaaaagcacg tcaccagcca 840 gcgagaaggc agaccctgga gcagtcaagg acaaggccagccctgagcct gagaaggact 900 tttccgaaaa ggcaaaacct tcacctcacc ccataaaggataaactgaag ggaaaagatg 960 agacggattc cccaacagtc catttgggcc tggactctgattcagagagc gaacttgtca 1020 tagatttagg agaagaccat tctgggcggg agggtcgaaaaaataagaag gaacccaaag 1080 aaccatctcc caaacaggat gttgtaggta aaactccaccatccacgacg gtgggcagcc 1140 attctccccc ggaaacaccg gtgctcaccc gctcttccgcccaaacttcc gcggctggcg 1200 ccacagccac caccagcacg tcctccacgg tcaccgtcacggccccggcc cccgccgcca 1260 caggaagccc agtgaaaaag cagaggccgc ttttaccgaaggagactgcc ccggccgtgc 1320 agcgggtcgt gtggaactca tcaactgtcc agcagaaggagatcacacag agcccatcca 1380 cgtccaccat caccctggtg accagcacac agtcatcggccctggtcacc agctcggggt 1440 ccatgagcac ccttgtgtcc tcagtcaacg ctgacctgcccatcgccact gcctcagctg 1500 atgtcgccgc tgatattgcc aagtacacta gcaaaatgatggatgcaata aaaggaacaa 1560 tgacagaaat atacaacgat ctttctaaaa acactactggaagcacaata gctgagattc 1620 gcaggctgag gatcgagata gagaagctcc agtggctgcaccagcaagag ctctccgaaa 1680 tgaaacacaa cttagagctg accatggcgg agatgcggcagagcctggag caggagcggg 1740 accggctcat cgccgaggtg aagaagcagc tggagttggagaagcagcag gcggtggatg 1800 agaccaagaa gaagcagtgg tgcgccaact gcaagaaggaggccatcttt tactgctgtt 1860 ggaacactag ctactgtgac tacccctgcc agcaagcccactggcctgag cacatgaagt 1920 cctgcaccca gtcagctact gctcctcagc aggaagcggatgctgaggtg aacacagaaa 1980 cactaaataa gtcctcccag gggagctcct cgagcacacaatcagcacct tcagaaacgg 2040 ccagcgcctc caaagagaag gagacgtcag ctgagaaaagcaaggagagt ggctcgaccc 2100 ttgacctttc tggctccaga gagacgccct cctccattctcttaggctcc aaccaaggct 2160 ctgaccattc ccggagtaat aaatccagtt ggagcagcagtgatgagaag aggggatcga 2220 cacgttccga tcacaacacc agtaccagca cgaagagcctcctcccgaaa gagtctcggc 2280 tggacacctt ctgggactag cagtgaatcg ggacacaaaccacccacccc attgggagaa 2340 aaacccagac gccaggaaaa gaagaaacaa caaaggcaggagaacagcca ctttcagact 2400 tgaaaatgac aaaaccctca gttgagcctg agcccccggcgcgggggctg ctacactaca 2460 ggacacccag catcggcttt gactgcagac tgttcacccacacgagccct gtgcttttgg 2520 tgtaaataat gtacaatttg tggatgtcat tgaatctagaggactttccc ctttttatat 2580 ttgtattaac tttaacttat taaaaaaaaa aaaaaaaaaa2620 16 2830 DNA Homo sapiens 16 aattcggcac gaggagagct ggttgcgtgagtctcctcag ctctgcttac cggtgcgact 60 agcggcagcg acgcggctaa aagcgaaggggcgagtgcga gtcccctgag ctgtacgaac 120 gcggtcgcca tggaccgccc agatgaggggcctccggcca agacccgccg cctgagcagc 180 tccgagtctc cacagcgcga cccgcccccgccgccgccgc cgccgccgct cctccgactg 240 ccgctgcctc caccccagca gcgcccgaggctccaggagg aaacggaggc ggcacaggtg 300 ctggccgata tgaggggggt gggactgggccccgcgctgc ccccgccgcc tccctatgtc 360 attctcgagg agggggggat ccgcgcatacttcacgctcg gtgctgagtg tcccggctgg 420 gattctacca tcgagtcggg gtatggggaggcgcccccgc ccacggagag cctggaagca 480 ctccccactc ctgaggcctc gggggggagcctggaaatcg attttcaggt tgtacagtcg 540 agcagttttg gtggagaggg ggccctagaaacctgtagcg cagtggggtg ggcgccccag 600 aggttagttg acccgaagag caaggaagaggcgatcatca tagtggagga tgaggatgag 660 gatgagcggg agagtatgag gagcagcaggaggcggcggc ggcggcggag gaggaagcag 720 aggaaggtga agagggaaag cagagagagaaatgccgaga ggatggagag catcctgcag 780 gcactggagg atattcagct ggatctggaggcagtgaaca tcaaggcagg caaagccttc 840 ctgcgtctca agcgcaagtt catccagatgcgaagaccct tcctggagcg cagagacctc 900 atcatccagc atatcccagg cttctgggtcaaagcattcc tcaaccaccc cagaatttca 960 attttgatca accgacgtga tgaagacattttccgctact tgaccaatct gcaggtacag 1020 gatctcagac atatctccat gggctacaaaatgaagctgt acttccagac taacccctac 1080 ttcacaaaca tggtgattgt caaggagttccagcgcaacc gctcaggccg gctggtgtct 1140 cactcaaccc caatccgctg gcaccggggccaggaacccc aggcccgtcg tcacgggaac 1200 caggatgcga gccacagctt tttcagctggttctcaaacc atagcctccc agaggctgac 1260 aggattgctg agattatcaa gaatgatctgtgggttaacc ctctacgcta ctacctgaga 1320 gaaaggggct ccaggataaa gagaaagaagcaagaaatga agaaacgtaa aaccaggggc 1380 agatgtgagg tggtgatcat ggaagacgcccctgactatt atgcagtgga agacattttc 1440 agcgagatct cagacattga tgagacaattcatgacatca agatctctga cttcatggag 1500 accaccgact acttcgagac cactgacaatgagataactg acatcaatga gaacatctgc 1560 gacagcgaga atcctgacca caatgaggtccccaacaacg agaccactga taacaacgag 1620 agtgctgatg accacgaaac cactgacaacaatgagagtg cagatgacaa caacgagaat 1680 cctgaagaca ataacaagaa cactgatgacaacgaagaga accctaacaa caacgagaac 1740 acttacggca acaacttctt caaaggtggcttctggggca gccatggcaa caaccaggac 1800 agcagcgaca gtgacaatga agcagatgaggccagtgatg atgaagataa tgatggcaac 1860 gaaggtgaca atgagggcag tgatgatgatggcaatgaag gtgacaatga aggcagcgat 1920 gatgacgaca gagacattga gtactatgagaaagttattg aagactttga caaggatcag 1980 gctgactacg aggacgtgat agagatcatctcagacgaat cagtggaaga agagggcatt 2040 gaggaaggca tccagcaaga tgaggacatctatgaggaag gaaactatga ggaggaagga 2100 agtgaagatg tctgggaaga aggggaagattcggacgact ctgacctaga ggatgtgctt 2160 caggtcccaa acggttgggc caatccggggaagaggggga aaaccggata agggttttcc 2220 ccttttgggg atcacctctc tgtatcccccacccactatc ccatttgccc tcctcctcag 2280 ctagggccac gcggccccac attgcacttctggggggtga ccgacttcgt acacgggttt 2340 aaagtttatt tttatggttt agtcattgcagagttcttat tttgggggga gggaaagggg 2400 gctagtcccc ttcttttggc cctccgcccccgcaggcttc tgtgtgctgc taactgtatt 2460 tattgtgatg ccttggtcag ggcccctctacccacttctc ccagtcagtt gtggccccag 2520 cccctctccc tgtgctgtgt ggagtggacaccctgacccc cgaagcgggg agggccgctg 2580 tggccttcgt cacagccgcg cagtgcccatggaggcgctg ctgccacctt cctctcccaa 2640 gttctttctc catccctctc ctcttcccgccgcgccgcta gcccgcctcg gtgtctatgc 2700 aaggccgctt cgccattgcg gtattctttgcggtattctt gtccccgtcc cccagaaggc 2760 tcgcctctcc ccgtggaccc tgttaatcccaataaaattc tgagcaagtt caaaaaaaaa 2820 aaaaaaaaaa 2830 17 2100 DNA Homosapiens 17 agagaatcca gaaagtgatg gagagccagt agtggaagat ggaacttctgtaaaaacact 60 ggaaacactc cagcaaagag tgaagcgtca agagaaccta cttaagcgttgtaaggaaac 120 aattcagtca cataaggaac aatgtacact attaactagt gaaaaagaagctctgcaaga 180 acaactggat gaaagacttc aagaactaga aaagataaag gaccttcatatggccgagaa 240 gactaaactt atcactcagt tgcgtgatgc aaagaactta attgaacagcttgaacaaga 300 taagggaatg gtaatcgcag agacaaaacg tcagatgcat gaaaccctggaaatgaaaga 360 agaagaaatt gctcaactcc gtagtcgcat caaacagatg actacccagggagaggaatt 420 acgggaacag aaagaaaagt ccgaaagagc tgcttttgag gaacttgaaaaagctttgag 480 tacagcccaa aaaacagagg aagcacggag aaaactgaag gcagaaatggatgaacaaat 540 aaaaactatc gaaaaaacaa gtgaggagga acgcatcagt cttcaacaggaattaagtcg 600 ggtgaaacag gaggttgttg atgtaatgaa aaaatcctca gaagaacaaattgctaagct 660 acagaagctt catgaaaagg agctggccag aaaagagcag gaactgaccaagaagcttca 720 gacccgagaa agggaatttc aggaacaaat gaaagtagct cttgaaaagagtcaatcaga 780 atatttgaag atcagccaag aaaaagaaca gcaagaatct ttggccctagaagagttaga 840 gttgcagaaa aaagcaatcc tcacagaaag tgaaaataaa cttcgggaccttcagcaaga 900 agcagagact tacagaacta gaattcttga attggaaagt tctttggaaaaaagcttaca 960 agaaaacaaa aatcagtcaa aagatttggc tgttcatctg gaagctgaaaaaaataagca 1020 caatatggag attacagtca tggttgaaaa acacaagaca gaattggaaagccttaagca 1080 tcagcaggat gccctttgga ctgaaaaact ccaagtctta aagcaacaatatcagactga 1140 aatggaaaaa cttagggaaa agtgtgaaca agaaaaagaa acattgttgaaagacaaaga 1200 gattatcttc caggcccaca tagaagaaat gaatgaaaag actttagaaaagcttgatgt 1260 gaagcaaaca gaactagaat cattatcttc tgaactgtca gaagtattaaaagcccgtca 1320 caaactagaa gaggaacttt ctgttctgaa agatcaaaca gataaaatgaagcaggaatt 1380 agaggccaag atggatgaac agaaaaatca tcaccagcag caagttgacagtatcattaa 1440 agaacacgag gtatctatcc agaggactga gaaggcatta aaagatcaaattaatcaact 1500 tgagcttctc ttgaaggaaa gggacaagca tttgaaagag catcaggctcatgtagaaaa 1560 tttagaggca gatattaaaa ggtctgaagg ggaactccag caggcatctgctaagctgga 1620 cgtttttcag tcttaccaga gtgccacaca tgagcagaca aaagcatatgaggaacagtt 1680 ggcccaattg cagcagaagt tgttggattt ggaaacagaa agaattcttcttaccaaaca 1740 ggttgctgaa gttgaagcac aaaagaaaga tgtttgtact gagttagatgctcacaaaat 1800 ccaggtgcag gacttaatgc agcaacttga aaaacaaaat agtgaaatggagcaaaaagt 1860 aaaatcttta acccaagtct atgagtccaa acttgaagat ggtaacaaagaacaggaaca 1920 gacaaagcaa atcttggtgg aaaaggaaaa tatgatttta caaatgagagaaggacagaa 1980 gaaagaaatt gagatactca cacagaaatt gtcagccaag gaggacagtattcatatttt 2040 gaatgaggaa tatgaaacca aatttaaaaa aaaaaaaaaa aaaaaaaaaaaaaaaaaaaa 2100 18 5629 DNA Homo sapiens 18 cttaagtgca aggaactctgtgttgggagg aaaaatgtcc ttcttcaatt tccgtaagat 60 cttcaagttg gggagcgagaagaagaagaa gcagtacgaa cacgtgaaga gggacctgaa 120 ccccgaagac ttttgggagattataggaga actgggcgac ggagcctttg ggaaagtgta 180 caaggcccag aataaagagaccagtgtttt agctgctgca aaagtgattg acactaaatc 240 tgaagaagaa cttgaagattacatggtaga gattgacata ttagcatctt gtgatcaccc 300 aaatatagtc aagcttctagatgccttcta ttatgagaac aatctttgga tcctcattga 360 attttgtgca ggtggagcagtagatgctgt gatgcttgaa cttgagagac cattaactga 420 gtcccaaata caagtagtttgcaagcagac tttagatgca ttgaactact tacatgataa 480 taagatcatc cacagagatctgaaggctgg caacattctc tttaccttag atggagatat 540 caaattggcg gattttggagtatcagctaa aaacacgagg acaattcaaa gaagagattc 600 ctttattggt acaccatattggatggctcc tgaagtagtc atgtgtgaaa catctaagga 660 cagaccctat gactacaaagctgatgtttg gtccctgggt atcactttaa tagaaatggc 720 tgagatagaa ccacctcatcatgaattaaa tccaatgcga gtgctgctaa aaatagcaaa 780 atctgagcca cctacattagcacagccatc cagatggtct tcaaatttta aggactttct 840 aaagaaatgc ttagaaaagaatgtggatgc caggtggact acatctcagc tgctgcagca 900 tccctttgtt actgttgattccaacaaacc catccgagaa ttgattgcag aggcgaaggc 960 tgaagtaaca gaagaagttgaagatggcaa agaggaagat gaagaggagg aaacagaaaa 1020 ttctctgcca atacctgcaagtaagcgtgc atcttctgac cttagtatcg ccagctctga 1080 agaagataaa ctttcacaaaatgcttgtat tttggagtct gtctcagaaa aaacagaacg 1140 tagtaactct gaagataaactcaacagcaa aattcttaat gaaaaaccca ccactgatga 1200 acctgaaaag gctgtggaggatattaatga acatattacc gatgctcagt tagaagcaat 1260 gactgaactc catgacagaacagcagtaat caaggagaat gaaagagaga agaggcccaa 1320 gcttgaaaat ctgcctgacacagaagacca agaaactgtg gacattaatt cagtcagtga 1380 aggaaaagag aataatataatgataacctt agaaacaaat attgaacata atctaaaatc 1440 tgaggaagaa aaggatcaggaaaagcaaca gatgtttgaa aataagctta taaaatctga 1500 agaaattaaa gatactattttgcaaacagt agatttagtt tctcaagaga ctggagaaaa 1560 agaggcaaat attcaggcagttgatagtga agttgggctt acaaaggaag acacccaaga 1620 gaaattgggg gaagacgacaaaactcaaaa agatgtgatc agcaatacaa gtgatgtgat 1680 aggaacatgt gaggcagcagatgtggctca gaaagtggat gaagacagtg ctgaggatac 1740 gcagagtaat gatgggaaagaagtggtcga agtaggccag aaattaatta ataagcccat 1800 ggtgggtcct gaggctggtggtactaagga agttcctatt aaagaaatag ttgaaatgaa 1860 tgaaatagaa gaaggtaaaaataaggaaca agcaataaac agttcagaga acataatgga 1920 catcaatgag gaaccaggaacaactgaagg tgaagaaatc actgagtcaa gtagcactga 1980 agaaatggag gtcagaagtgtggtggctga tactgaccaa aaggctttag gaagtgaagt 2040 tcaggatgct tctaaagtcactactcagat agataaagag aaaaaagaaa ttccagtgtc 2100 aattaaaaaa gagcctgaagttactgtagt ttcacagccc actgaacctc agcctgttct 2160 aatacccagt attaatatcaactctgacag tggagaaaat aaagaagaaa taggttcttt 2220 atcaaaaact gaaactattctgccaccaga atctgagaat ccaaaggaaa atgataatga 2280 ttcaggcact ggttccactgctgatactag cagtattgac ttgaatttat ccatctctag 2340 ctttctaagt aaaactaaagacagtggatc gatatcttta caagaaacaa gaagacaaaa 2400 gaaaacattg aagaaaacacgcaaatttat tgttgatggt gtagaagtga gtgtaacaac 2460 atcaaagata gttacagatagtgattccaa aactgaagaa ttgcggtttc ttagacgtca 2520 ggaacttcgg gaattaagatttcttcagaa agaagagcaa agagcccaac aacagctcaa 2580 tagcaaacta cagcaacaacgagaacaaat tttccggcgc tttgagcagg aaatgatgag 2640 taaaaagcga caatatgaccaggaaattga gaatctagaa aaacagcaga aacagactat 2700 cgaacgcctg gaacaagagcacacaaatcg cttgcgagat gaagccaaac gcatcaaagg 2760 agaacaagag aaagagttgtccaaatttca gaatatgctg aagaaccgaa agaaggaggt 2820 tataaatgaa gtggagaaagcacccaaaga gctgagaaaa gagctcatga aacgcaggaa 2880 agaggagctt gcacaaagccagcatgctca ggaacaagag tttgttcaga aacaacagca 2940 agaattagat ggctctctgaaaaagatcat ccagcagcag aaggcagagt tagctaatat 3000 tgagagagag tgcctgaataacaagcaaca gctcatgaga gctcgagaag ctgcaatttg 3060 ggagctcgaa gaacgacacttacaagaaaa acaccagctg ctcaaacagc agcttaaaga 3120 tcagtatttc atgcaaagacatcagctact taagcgccac gagaaggaaa cagagcaaat 3180 gcagcgttac aatcaaagacttattgagga attgaaaaac agacagactc aagaaagagc 3240 aagactgccc aagattcagcgcagtgaagc caagactcga atggccatgt ttaagaagag 3300 tttgagaatt aactcaacagccacaccaga tcaggaccgt gataaaatta aacagtttgc 3360 tgcacaagaa gaaaagaggcagaaaaatga gagaatggct cagcatcaga aacatgagaa 3420 tcaaatgcga gatcttcagttgcagtgtga agccaatgtc cgcgaactgc atcagctgca 3480 gaatgaaaaa tgccacttgttggttgagca tgagactcag aaactgaagg agttagatga 3540 ggaacatagc caagaattaaaggagtggag agagaaattg agacctagga aaaagacact 3600 ggaagaagag tttgccaggaaactacagga acaggaagta ttctttaaaa tgactgggga 3660 gtctgaatgc cttaacccatcaacacagag ccggatttcc aaattttatc ctattcccag 3720 cttgcattcc accggatcataacaaaggga agcattctgt gcgtgggttt ggctctttca 3780 gtatgtcatt ctgttctcatcttctgccac agtctctcag atagctcatg aagacaatca 3840 cctgcctcac cttctaggtgttttcctttt ttgttttttt tgttttgttt tgtttttaag 3900 caaagatgaa gggaaaacgaactaagacag acgctaggcc atgttggcaa agtagcatct 3960 tggtgactaa ggtgactttgtatattcatc ttaaaaatta tgttctttag acactgctac 4020 ctgaaaactg ttggagaaataatgtttaaa gttatttaag aaaaactgtt acatcactaa 4080 gtattaataa attcttcttacctgacgtaa cttctcaatg cctaaattct gtagttgaag 4140 ctctgctgca gagagttgggataattttct tttggtggat cagctctcat aaaaaagcta 4200 tgatttgctc aaatatgctgttgactcagt aaatgaatat atttttttct ttaaatagga 4260 acaacctctt ttaaaagagaaaaattattt cagtgatttg tcaaaacgaa ttacctcttt 4320 tggcatgagc taataattgagggtgctaat tttcttaaga tagtgcctaa aacactaaat 4380 ttcagtcaag tcgtaagtaggattttcttt ttgatcaaca gggacaaaaa catctttaga 4440 attaaaaaca tggttgttttggaatttttg cttctcttac cgtttgatag aaattttcat 4500 cctaaaatac atgtacaaagtttggaaaga tgaaaaaaag aggtagcttt tagattgcaa 4560 attggaaatg taaaactcatgaaatttaag caatataggt ttagctatct gtgtttattt 4620 tctaaaataa tacctgagctggttaaatga tttctctcca tcttagctaa ttctgtttaa 4680 aactctgtca gaggcctgcaggctgtgagt tatatttata aatatatctt cagaaattaa 4740 tcttaaaaga ggcattagttcagaatactt ttttaaaagt ttaaattaaa tatttaggca 4800 cgtcagaaat tacttttccttattttgaaa tgaggctact tatgtcttgg ttttattttg 4860 ttccatgttt aaatcattcactttgatttg agtgggaaaa gcctgaagcc tttatcatgt 4920 ggttgctggt gtgtgtaattattaatgaaa tgttcactcc tagtccctta tgaggcttag 4980 aatttcaacc acgtgtcaggtcagacagta ttataaactg tactttgctg tctgagacag 5040 cacatttgtg aatgatgcttgctgcctgcc attttcaacc tattctctct taagagtgct 5100 aggtaccaaa ttgtgaaagtttgttttcag ttatattact tttgaggctg gtgaaaaatt 5160 taaatgtaac tttgtgggaacactgattca tatttagaaa atgtaaatgt ctgtagcact 5220 ttcttgcagt taatttgaaaactttggatg ctgaaccttg tttgtcagtg atttagatga 5280 tttaaaaatg catgtgtgatttgaatttta taattgtttt gacaagcata atttacttgg 5340 acaacttcgt aggtagccttaacttctggc caagtttgtt ttttatataa atatatatac 5400 atatatacat attatgtatggttgtaaatt catacactta tcacatgaat gtgttactgt 5460 atacaaaact cttaatgctttattctcaaa tgctgggttg aaaaatgttt tgaaagcctt 5520 ttaaaatata tatctttataaagtaatatt caggatgatg ataaaaattg tttatattgt 5580 tatgataaaa atgacagtataatgttaaaa aaaaaaaaaa aaaaaaaaa 5629 19 1991 DNA Homo sapiens 19aaaacgcttt ttgcatacaa gcaggaaaat gagatgttat ccagtagtag agatcagaga 60gttgtgacat ctgaggacca agttcaagaa gggactaaag tgctgaaact taaaacaaaa 120atggctgata aagaaaacat gaagagacct gcagagagca aaaataatac agtggtgggg 180aaacattgta ttcctttaaa accttcaaat gaactaacca attcaactgt agtaattgac 240acacataaac ctaaggatag taatcaaact ccgcatttgt tactaactga agatgatccc 300caaagtcaac atatgacatt aagccaggca tttcacctta aaaacaatag taaaaagaaa 360caaatgacta cagaaaaaca aaagcaagat gctaacatgc ccaagaaacc tgtgcttgga 420tcttatcgtg gccagattgt tcagtctaag attaattcat ttagaaaacc tctacaagtc 480aaagatgaga gttctgcagc aacaaagaaa ctttcagcca ctatacctaa agccacaaaa 540cctcagcctg taaacaccag cagtgtaaca gtgaaaagta atagatcctc caataagact 600gccactacta aatttgtgag cactacatct cagaacacac aacttgtgcg acctcctatt 660agaagtcatc acagtaatac ccgggacact gtgaaacaag gcatcagtag aacctctgcc 720aatgttacaa tccggaaagg gcctcatgaa aaagaactat tacaatcaaa aacagcttta 780tctagtgtca aaaccagttc ttctcaaggt ataataagaa ataagactct atcaagatcc 840atagcatctg aagttgtagc caggcctgct tcattgtcta atgataaact gatggaaaag 900tcagagcccg ttgaccagcg aagacatact gcaggaaaag caattgttga tagtagatca 960gctcagccca aagaaacctc ggaagagaga aaagctcgtc tgagtgagtg gaaagctggc 1020aaaggaagag tgctaaaaag gccccctaat tcagtagtta ctcagcatga gcctgcagga 1080caaaatgaaa aaccagttgg gtctttttgg actaccatgg cagaagaaga tgaacaaaga 1140ttatttactg aaaaagtaaa caacacattt tctgaatgcc tgaacttgat taatgaggga 1200tgtccaaaag aagatatact ggtcacactg aatgacctga ttaaaaatat tccagatgcc 1260aaaaagcttg ttaagtattg gatatgtctt gcacttattg aaccaatcac aagtcctatt 1320gaaaatatta ttgcaatcta tgagaaagcc attctggcag gggctcagcc tattgaagag 1380atgcgacaca cgattgtaga tattctaaca atgaagagtc aagaaaaagc taatttagga 1440gaaaatatgg agaagtcttg tgcaagcaag gaagaagtca aagaagtcag tattgaagat 1500acaggtgttg atgtagatcc agaaaaactg gaaatggaga gtaaacttca tagaaatttg 1560ctatttcaag attgtgaaaa agagcaagac aacaaaacaa aagatccaac ccatgatgtt 1620aaaaccccca atacagaaac gaggacaagt tgcttaatta aatataatgt gtctactacg 1680ccatacttgc aaagtgtgaa aaaaaaaggt gcagtttgat ggaacaaatt ccgcatttaa 1740agagctgaag tttttaacac cagtgagacg ttctcgacgt cttcaagaga aaacttctaa 1800attgccagat atgttaaaag atcattatcc ttgtgtgtct tcattggaac agctaacgga 1860gttgggaaga gaaactgatg cttttgtatg ccgccctaat gcagcactgt gccgggtgta 1920ctatgaggct gatacaacat aagagaaata aagctctgtt agggaaaaaa aaaaaaaaaa 1980aaaaaaaaaa a 1991 20 3462 DNA Homo sapiens 20 cagatgtatt aaaaatagctcagtttttac aattttcttt gattcagtgt cgaaaggaat 60 tcaaaaatat aagcgccataaattttcatt ctgttgttga aaagtatgta agtgaatttt 120 ttaagcgagg ttttggttcaggtaaacgag agtttattat gtttccatat gattcacgat 180 tagatgataa aaaattcttatactcagctc ccagaaataa atcccatatt gatacttgtt 240 tgcatgccta tatttttcggcctgaagtgt atcagttacc tatttgtaaa ttaaaagaac 300 tatttgaaga aaatagaaaacttcagcagt ttagtccact ttcagattat gaaggtcaag 360 aagaagaaat gaatggtacaaaaatgaaat ttggaaaacg aaataactca agaggtgaag 420 ccattatatc tggaaagcaaagatcatctc attctttgga ttatgataag gatagagtca 480 aagaattgat taatttaattcagtgtagga aaaagagtgt gggtggggac tcagacacag 540 aagatatgag aagcaaaactgtcttgaaga ggaagcttga ggatctacct gaaaatatga 600 gaaagctcgc caaaaccagtaatttatctg aaaattgcca tctgtatgaa gagtctccac 660 agcctattgg ctcacttggacatgatgctg acttgaggcg gcagcagcag gatacctgta 720 actccggcat tgctgacatccataggctgt ttaattggtt atcagaaaca ctagcaaatg 780 cgcgccattc tgatgcatctctgacagaca cagtcaacaa agccttagga ttgagcactg 840 atgatgccta tgaagagctgaggcaaaaac atgagtatga gttgaactct accccagata 900 agaaagacta tgagcagcctacttgtgcaa aagttgaaaa tgcacagttt aagggtactc 960 agagcttatt actagaagttgatgcaacat ctaagtattc tgttgctatt tctaccagcg 1020 aagtgggcac tgaccataagctacatttga aagaagatcc aaatttaatt agcgtgaata 1080 attttgaaga ttgcagtttgtgtcccagtg ttcccattga acatggattt cgtagacaac 1140 agtctaagtc aaataatgttgaagagactg aaatacattg gaaactgatt ccaattacag 1200 acacactaaa gggcaccactgaggatgacg tgttgacagg tcaggtggag gagcagtgtg 1260 tgccagcagc agaggcagagccgcctgcag tgagcgaaac cacagagagg acagtgttag 1320 gagagtacaa tctcttttctaggaagatag aagagatttt gaagcaaaag aatgtttcat 1380 atgtcagtag agtttccacacctatctttt caacacaaga gaagatgaaa cggctttccg 1440 agttcatata ttctaagacttccaaagctg gtgtgcagga gtttgtagat ggtttgcatg 1500 agaagctaaa tactattattattaaagcat cagccaaggg tgggaatttg ccaccagtca 1560 gtcctaacga ttctggtgctaagatagcat cgaatcctct ggaaaggcat gtcataccag 1620 tttcctcaag tgacttcaacaataaacatc tccttgagcc actgtgtagt gatcctttga 1680 aagataccaa ctctgatgagcagcattcca cttcggcttt aactgaagta gaaatgaacc 1740 agcctcaaca tgccacagagttaatggtga cttctgatca tattgtacct ggtgatatgg 1800 cccgggaacc agtagaagaaacaacaaaat cccccagtga tgtaaacatt tctgctcagc 1860 cagctctttc aaattttataagccagttag aacctgaagt atttaatagt ttggttaaaa 1920 tcatgaaaga cgtccagaaaaatactgtga aattttatat tcatgaagaa gaagagagtg 1980 tgctctgtaa agaaataaaggaatatctta tcaaattagg caatacagaa tgtcatcctg 2040 aacagttttt ggaaagaagatcaaaattag ataaactatt gattattatt caaaatgaag 2100 acattgcagg tttcattcacaagatacctg gcttggtgac tttaaagaag ctcccctgtg 2160 ttagttttgc tggtgttgatagcctggatg atgttaaaaa tcatacatac aatgaattat 2220 ttgtatctgg aggttttatcgtatctgatg aatcaattct aaacccagag gttgtcacag 2280 ttgagaacct taaaaattttttgacattcc ttgaggaact tagtactcca gaaggaaaat 2340 ggcaatggaa agtccactgtaaatttcaga agaaactaaa ggaactaggc agattgaatg 2400 ctaaagctct aagtctgttgacgcttctga atgtctatca gaagaaacat ctggttgaaa 2460 ttttgtcata ccacaattgtgattcacaaa ctcgaaatgc tccagaattg gattgcctta 2520 tcagacttca ggctcagaacatacagcaac gacacgtagt ctttttaaca gagaagaaca 2580 tcaagatgct ttccagttatacagataatg gaatagtggt tgcaactgct gaagacttca 2640 tgcaaaactt taaaaatcttgtgggctatc acaattcaat cacagaagaa aaccttccac 2700 agcttggtgc taatgagaatcttgagtcgc agtcagctct tttagaaaac gatgaaaagg 2760 atgaagagga tatgtctctggattcagggg atgaaatctc acatatagaa gtatgcagca 2820 attttcattc agaaatatgggagaaagaga ccaaaggatc acgtggaaca gatcaaaaaa 2880 agaatactca aattgagttgcaatcgtctc ctgatgtgca aaacagttta ttagaagata 2940 agacttacct tgattctgaagagagaactt ctattgatat agtatgctct gaaggagaga 3000 acagcaattc aacagaacaagattcatata gtaactttca ggtttatcat agtcaattaa 3060 atatgtccca tcagtttagtcattttaatg ttctcactca tcagacattt ttggggacac 3120 catatgccct ttcatcaagtcagtctcaag aaaatgagaa ttacttctta tctgcttata 3180 ctgaaagctt ggatagagataaatctccac ctcccttaag ttgggggaaa agtgattctt 3240 ccaggccata ttcacaagagaaataactgt agtaactttt tttttaagag attgttgtgg 3300 actttgttta ttaacaatttatatttcatt ctctaaacaa aaggttcttg ttctttctca 3360 aatgtttttt cttttatttaaatcatgatg gcctgtaaca gttgaagcat ctaaaaattg 3420 aaataaatat atatttttaacataaaaaaa aaaaaaaaaa aa 3462 21 1368 DNA Homo sapiens 21 aattcggcacgaggggagcg cagcagccat ggcaagccgt ctcctgctca acaacggcgc 60 caagatgcccatcctggggt tgggtacctg gaagtcccct ccagggcagg tgactgaggc 120 cgtgaaggtggccattgacg tcgggtaccg ccacatcgac tgtgcccatg tgtaccagaa 180 tgagaatgaggtgggggtgg ccattcagga gaagctcagg gagcaggtgg tgaagcgtga 240 ggagctcttcatcgtcagca agctgtggtg cacgtaccat gagaagggcc tggtgaaagg 300 agcctgccagaagacactca gcgacctgaa gctggactac ctggacctct accttattca 360 ctggccgactggctttaagc ctgggaagga atttttccca ttggatgagt cgggcaatgt 420 ggttcccagtgacaccaaca ttctggacac gtgggcggcc atggaagagc tggtggatga 480 agggctggtgaaagctattg gcatctccaa cttcaaccat ctccaggtgg agatgatctt 540 aaacaaacctggcttgaagt ataagcctgc agttaaccag attgagtgcc acccatatct 600 cactcaggagaagttaatcc agtactgcca gtccaaaggc atcgtggtga ccgcctacag 660 ccccctcggctctcctgaca ggccctgggc caagcccgag gacccttctc tcctggagga 720 tcccaggatcaaggcgatcg cagccaagca caataaaact acagcccagg tcctgatccg 780 gttccccatgcagaggaact tggtggtgat ccccaagtct gtgacaccag aacgcattgc 840 tgagaactttaaggtctttg actttgaact gagcagccag gatatgacca ccttactcag 900 ctacaacaggaactggaggg tctgtgcctt gttgagctgt acctcccaca aggattaccc 960 cttccatgaagagttttgaa gctgtggttg cctgctcgtc cccaagtgac ctatacctgt 1020 gtttcttgcctcattttttt ccttgcaaat gtagtatggc ctgtgtcact cagcagtggg 1080 acagcaacctgtagagtggc cagcgagggc gtgtctagct tgatgttgga tctcaagagc 1140 cctgtcagtagagtagaagt ctcttccagt ttgctttgcc cttctttcta ccctgctggg 1200 gaaagtacaacctgaatacc cttttctgac caaagagaag caaaatctac caggtcaaaa 1260 tagtgccactaacggttgag ttttgactgc ttggaactgg aatcctttca gcaagacttc 1320 tctttgcctcaaataaaaag tgcttttgtg aaaaaaaaaa aaaaaaaa 1368 22 398 DNA Homo sapiensmodified_base (1) a, t, c, g, other or unknown 22 ngthctbrty nchckaattcggcacgaggc tgcggacata aatcttaaag ctagtaacat 60 gttgttcttc taggaattccattcagctac agatttaagg tttatcagta gtatttccag 120 aaagatggtc cgacacagtggctcacgttt ataatcccag cactttggga ggccgaggtg 180 ggtgaattgc ttgagtccaggagttcaaga ccagcctggg caacatggca aaaccctgtc 240 tttgcctgta gtacccccagctatttgaga ggctgaggtg gaagaatcac ctgagcctgg 300 ggaggtcagg gctgcagtgtgctgaaattg cacaactgca ctccagcctg ggcaatcaga 360 gtgagaccct gtctttaagaaaaaaaaaaa aaaaaaaa 398 23 685 PRT Homo sapiens 23 Met Cys Gln Ile GluAla Ser Ala Lys Glu His Glu Ala Glu Ile Asn 1 5 10 15 Lys Leu Asn GluLeu Lys Glu Asn Leu Val Lys Gln Cys Glu Ala Ser 20 25 30 Glu Lys Asn IleGln Lys Lys Tyr Glu Cys Glu Leu Glu Asn Leu Arg 35 40 45 Lys Ala Thr SerAsn Ala Asn Gln Asp Asn Gln Ile Cys Ser Ile Leu 50 55 60 Leu Gln Glu AsnThr Phe Val Glu Gln Val Val Asn Glu Lys Val Lys 65 70 75 80 His Leu GluAsp Thr Leu Lys Glu Leu Glu Ser Gln His Ser Ile Leu 85 90 95 Lys Asp GluVal Thr Tyr Met Asn Asn Leu Lys Leu Lys Leu Glu Met 100 105 110 Asp AlaGln His Ile Lys Asp Glu Phe Phe His Glu Arg Glu Asp Leu 115 120 125 GluPhe Lys Ile Asn Glu Leu Leu Leu Ala Lys Glu Glu Gln Gly Cys 130 135 140Val Ile Glu Lys Leu Lys Ser Glu Leu Ala Gly Leu Asn Lys Gln Phe 145 150155 160 Cys Tyr Thr Val Glu Gln His Asn Arg Glu Val Gln Ser Leu Lys Glu165 170 175 Gln His Gln Lys Glu Ile Ser Glu Leu Asn Glu Thr Phe Leu SerAsp 180 185 190 Ser Glu Lys Glu Lys Leu Thr Leu Met Phe Glu Ile Gln GlyLeu Lys 195 200 205 Glu Gln Cys Glu Asn Leu Gln Gln Glu Lys Gln Glu AlaIle Leu Asn 210 215 220 Tyr Glu Ser Leu Arg Glu Ile Met Glu Ile Leu GlnThr Glu Leu Gly 225 230 235 240 Glu Ser Ala Gly Lys Ile Ser Gln Glu PheGlu Ser Met Lys Gln Gln 245 250 255 Gln Ala Ser Asp Val His Glu Leu GlnGln Lys Leu Arg Thr Ala Phe 260 265 270 Thr Glu Lys Asp Ala Leu Leu GluThr Val Asn Arg Leu Gln Gly Glu 275 280 285 Asn Glu Lys Leu Leu Ser GlnGln Glu Leu Val Pro Glu Leu Glu Asn 290 295 300 Thr Ile Lys Asn Leu GlnGlu Lys Asn Gly Val Tyr Leu Leu Ser Leu 305 310 315 320 Ser Gln Arg AspThr Met Leu Lys Glu Leu Glu Gly Lys Ile Asn Ser 325 330 335 Leu Thr GluGlu Lys Asp Asp Phe Ile Asn Lys Leu Lys Asn Ser His 340 345 350 Glu GluMet Asp Asn Phe His Lys Lys Cys Glu Arg Glu Glu Arg Leu 355 360 365 IleLeu Glu Leu Gly Lys Lys Val Glu Gln Thr Ile Gln Tyr Asn Ser 370 375 380Glu Leu Glu Gln Lys Val Asn Glu Leu Thr Gly Gly Leu Glu Glu Thr 385 390395 400 Leu Lys Glu Lys Asp Gln Asn Asp Gln Lys Leu Glu Lys Leu Met Val405 410 415 Gln Met Lys Val Leu Ser Glu Asp Lys Glu Val Leu Ser Ala GluVal 420 425 430 Lys Ser Leu Tyr Glu Glu Thr Ile Asn Ser Val Gln Lys LysLys Gln 435 440 445 Leu Ser Arg Asp Leu Glu Val Phe Leu Ser Gln Lys GluAsp Val Ile 450 455 460 Leu Lys Glu His Ile Thr Gln Leu Glu Lys Lys LeuGln Leu Met Val 465 470 475 480 Glu Glu Gln Asp Asn Leu Asn Lys Leu LeuGlu Asn Glu Gln Val Gln 485 490 495 Lys Leu Phe Val Lys Thr Gln Leu TyrGly Phe Leu Lys Glu Met Gly 500 505 510 Ser Glu Val Ser Glu Asp Ser GluGlu Lys Asp Val Val Asn Val Leu 515 520 525 Gln Ala Val Gly Glu Ser LeuAla Lys Ile Asn Glu Glu Lys Cys Asn 530 535 540 Leu Ala Phe Gln Arg AspGlu Lys Val Leu Glu Leu Glu Lys Glu Ile 545 550 555 560 Lys Cys Leu GlnGlu Glu Ser Val Val Gln Cys Glu Glu Leu Lys Ser 565 570 575 Leu Leu ArgAsp Tyr Glu Gln Glu Lys Val Leu Leu Arg Lys Glu Leu 580 585 590 Glu GluIle Gln Ser Glu Lys Glu Ala Leu Gln Ser Asp Leu Leu Glu 595 600 605 MetLys Asn Ala Asn Glu Lys Thr Arg Leu Glu Asn Gln Asn Leu Leu 610 615 620Ile Gln Val Glu Glu Val Ser Gln Thr Cys Ser Lys Ser Glu Ile His 625 630635 640 Asn Glu Lys Glu Lys Cys Phe Ile Lys Glu His Glu Asn Leu Lys Pro645 650 655 Leu Leu Glu Gln Lys Glu Leu Arg Asp Arg Arg Ala Glu Leu IleLeu 660 665 670 Leu Lys Asp Ser Leu Ala Lys Ser Pro Tyr Cys Lys Lys 675680 685 24 1075 PRT Homo sapiens 24 Met Cys Val Met Leu Val Ser Asn LeuPro Asn Lys Gly Tyr Ser Val 1 5 10 15 Glu Glu Val Tyr Asp Leu Ala LysPro Phe Gly Gly Leu Lys Asp Ile 20 25 30 Leu Ile Leu Ser Ser His Lys LysAla Tyr Ile Glu Ile Asn Arg Lys 35 40 45 Ala Ala Glu Ser Met Val Lys PheTyr Thr Cys Phe Pro Val Leu Met 50 55 60 Asp Gly Asn Gln Leu Ser Ile SerMet Ala Pro Glu Ser Met Asn Ile 65 70 75 80 Lys Asp Glu Glu Ala Ile PheIle Thr Leu Val Lys Glu Asn Asp Pro 85 90 95 Glu Ala Asn Ile Asp Thr IleTyr Asp Arg Phe Val His Leu Asp Asn 100 105 110 Leu Pro Glu Asp Gly LeuGln Cys Val Leu Cys Val Gly Leu Gln Phe 115 120 125 Gly Lys Val Asp HisHis Val Phe Ile Ser Asn Arg Asn Lys Ala Ile 130 135 140 Leu Gln Leu AspSer Pro Glu Ser Ala Gln Ser Met Tyr Ser Phe Leu 145 150 155 160 Lys GlnAsn Pro Gln Asn Ile Gly Asp His Met Leu Thr Cys Ser Leu 165 170 175 SerPro Lys Ile Asp Leu Pro Glu Val Gln Ile Glu His Asp Pro Glu 180 185 190Leu Glu Lys Glu Ser Pro Gly Leu Lys Asn Ser Pro Ile Asp Glu Ser 195 200205 Glu Val Gln Thr Ala Thr Asp Ser Pro Ser Val Lys Pro Asn Glu Leu 210215 220 Glu Glu Glu Ser Thr Pro Ser Ile Gln Thr Glu Thr Leu Val Gln Gln225 230 235 240 Glu Glu Pro Cys Glu Glu Glu Ala Glu Lys Ala Thr Cys AspSer Asp 245 250 255 Phe Ala Val Glu Thr Leu Glu Leu Glu Thr Gln Gly GluGlu Val Lys 260 265 270 Glu Glu Ile Pro Leu Val Ala Ser Ala Ser Val SerIle Glu Gln Phe 275 280 285 Thr Glu Asn Ala Glu Glu Cys Ala Leu Asn GlnGln Met Phe Asn Ser 290 295 300 Asp Leu Glu Lys Lys Gly Ala Glu Ile IleAsn Pro Lys Thr Ala Leu 305 310 315 320 Leu Pro Ser Asp Ser Val Phe AlaGlu Glu Arg Asn Leu Lys Gly Ile 325 330 335 Leu Glu Glu Ser Pro Ser GluAla Glu Asp Phe Ile Ser Gly Ile Thr 340 345 350 Gln Thr Met Val Glu AlaVal Ala Glu Val Glu Lys Asn Glu Thr Val 355 360 365 Ser Glu Ile Leu ProSer Thr Cys Ile Val Thr Leu Val Pro Gly Ile 370 375 380 Pro Thr Gly AspGlu Lys Thr Val Asp Lys Lys Asn Ile Ser Glu Lys 385 390 395 400 Lys GlyAsn Met Asp Glu Lys Glu Glu Lys Glu Phe Asn Thr Lys Glu 405 410 415 ThrArg Met Asp Leu Gln Ile Gly Thr Glu Lys Ala Glu Lys Asn Glu 420 425 430Gly Arg Met Asp Ala Glu Lys Val Glu Lys Met Ala Ala Met Lys Glu 435 440445 Lys Pro Ala Glu Asn Thr Leu Phe Lys Ala Tyr Pro Asn Lys Gly Val 450455 460 Gly Gln Ala Asn Lys Pro Asp Glu Thr Ser Lys Thr Ser Ile Leu Ala465 470 475 480 Val Ser Asp Val Ser Ser Ser Lys Pro Ser Ile Lys Ala ValIle Val 485 490 495 Ser Ser Pro Lys Ala Lys Ala Thr Val Ser Lys Thr GluAsn Gln Lys 500 505 510 Ser Phe Pro Lys Ser Val Pro Arg Asp Gln Ile AsnAla Glu Lys Lys 515 520 525 Leu Ser Ala Lys Glu Phe Gly Leu Leu Lys ProThr Ser Ala Arg Ser 530 535 540 Gly Leu Ala Glu Ser Ser Ser Lys Phe LysPro Thr Gln Ser Ser Leu 545 550 555 560 Thr Arg Gly Gly Ser Gly Arg IleSer Ala Leu Gln Gly Lys Leu Ser 565 570 575 Lys Leu Asp Tyr Arg Asp IleThr Lys Gln Ser Gln Glu Thr Glu Ala 580 585 590 Arg Pro Ser Ile Met LysArg Asp Asp Ser Asn Asn Lys Thr Leu Ala 595 600 605 Glu Gln Asn Thr LysAsn Pro Lys Ser Thr Thr Gly Arg Ser Ser Lys 610 615 620 Ser Lys Glu GluPro Leu Phe Pro Phe Asn Leu Asp Glu Phe Val Thr 625 630 635 640 Val AspGlu Val Ile Glu Glu Val Asn Pro Ser Gln Ala Lys Gln Asn 645 650 655 ProLeu Lys Gly Lys Arg Lys Glu Thr Leu Lys Asn Val Pro Phe Ser 660 665 670Glu Leu Asn Leu Lys Lys Lys Lys Gly Lys Thr Ser Thr Pro Arg Gly 675 680685 Val Glu Gly Glu Leu Ser Phe Val Thr Leu Asp Glu Ile Gly Glu Glu 690695 700 Glu Asp Ala Ala Ala His Leu Ala Gln Ala Leu Val Thr Val Asp Glu705 710 715 720 Val Ile Asp Glu Glu Glu Leu Asn Met Glu Glu Met Val LysAsn Ser 725 730 735 Asn Ser Leu Phe Thr Leu Asp Glu Leu Ile Asp Gln AspAsp Cys Ile 740 745 750 Ser His Ser Glu Pro Lys Asp Val Thr Val Leu SerVal Ala Glu Glu 755 760 765 Gln Asp Leu Leu Lys Gln Glu Arg Leu Val ThrVal Asp Glu Ile Gly 770 775 780 Glu Val Glu Glu Leu Pro Leu Asn Glu SerAla Asp Ile Thr Phe Ala 785 790 795 800 Thr Leu Asn Thr Lys Gly Asn GluGly Asp Ile Val Arg Asp Ser Ile 805 810 815 Gly Phe Ile Ser Ser Gln ValPro Glu Asp Pro Ser Thr Leu Val Thr 820 825 830 Val Asp Glu Ile Gln AspAsp Ser Ser Asp Leu His Leu Val Thr Leu 835 840 845 Asp Glu Val Thr GluGlu Asp Glu Asp Ser Leu Ala Asp Phe Asn Asn 850 855 860 Leu Lys Glu GluLeu Asn Phe Val Thr Val Asp Glu Val Gly Glu Glu 865 870 875 880 Glu AspGly Asp Asn Asp Leu Lys Val Glu Leu Ala Gln Ser Lys Asn 885 890 895 AspHis Pro Thr Asp Lys Lys Gly Asn Arg Lys Lys Arg Ala Val Asp 900 905 910Thr Lys Lys Thr Lys Leu Glu Ser Leu Ser Gln Val Gly Pro Val Asn 915 920925 Glu Asn Val Met Glu Glu Asp Leu Lys Thr Met Ile Glu Arg His Leu 930935 940 Thr Ala Lys Thr Pro Thr Lys Arg Val Arg Ile Gly Lys Thr Leu Pro945 950 955 960 Ser Glu Lys Ala Val Val Thr Glu Pro Ala Lys Gly Glu GluAla Phe 965 970 975 Gln Met Ser Glu Val Asp Glu Glu Ser Gly Leu Lys AspSer Glu Pro 980 985 990 Glu Arg Lys Arg Lys Lys Thr Glu Asp Ser Ser SerGly Lys Ser Val 995 1000 1005 Val Ser Asp Val Pro Glu Glu Leu Asp PheLeu Val Pro Lys Ala Gly 1010 1015 1020 Phe Phe Cys Pro Ile Cys Ser LeuPhe Tyr Ser Gly Glu Lys Ala Met 1025 1030 1035 1040 Thr Asn His Cys LysSer Thr Arg His Lys Gln Asn Thr Glu Lys Phe 1045 1050 1055 Met Ala LysGln Arg Lys Glu Lys Glu Gln Asn Glu Ala Glu Glu Arg 1060 1065 1070 SerSer Arg 1075 25 852 PRT Homo sapiens 25 Met Lys Arg Ala Ala Ala Lys HisLeu Ile Glu Arg Tyr Tyr His Gln 1 5 10 15 Leu Thr Glu Gly Cys Gly AsnGlu Ala Cys Thr Asn Glu Phe Cys Ala 20 25 30 Ser Cys Pro Thr Phe Leu ArgMet Asp Asn Asn Ala Ala Ala Ile Lys 35 40 45 Ala Leu Glu Leu Tyr Lys IleAsn Ala Lys Leu Cys Asp Pro His Pro 50 55 60 Ser Lys Lys Gly Ala Ser SerAla Tyr Leu Glu Asn Ser Lys Gly Ala 65 70 75 80 Pro Asn Asn Ser Cys SerGlu Ile Lys Met Asn Lys Lys Gly Ala Arg 85 90 95 Ile Asp Phe Lys Asp ValThr Tyr Leu Thr Glu Glu Lys Val Tyr Glu 100 105 110 Ile Leu Glu Leu CysArg Glu Arg Glu Asp Tyr Ser Pro Leu Ile Arg 115 120 125 Val Ile Gly ArgVal Phe Ser Ser Ala Glu Ala Leu Val Gln Ser Phe 130 135 140 Arg Lys ValLys Gln His Thr Lys Glu Glu Leu Lys Ser Leu Gln Ala 145 150 155 160 LysAsp Glu Asp Lys Asp Glu Asp Glu Lys Glu Lys Ala Ala Cys Ser 165 170 175Ala Ala Ala Met Glu Glu Asp Ser Glu Ala Ser Ser Ser Arg Ile Gly 180 185190 Asp Ser Ser Gln Gly Asp Asn Asn Leu Gln Lys Leu Gly Pro Asp Asp 195200 205 Val Ser Val Asp Ile Asp Ala Ile Arg Arg Val Tyr Thr Arg Leu Leu210 215 220 Ser Asn Glu Lys Ile Glu Thr Ala Phe Leu Asn Ala Leu Val TyrLeu 225 230 235 240 Ser Pro Asn Val Glu Cys Asp Leu Thr Tyr His Asn ValTyr Ser Arg 245 250 255 Asp Pro Asn Tyr Leu Asn Leu Phe Ile Ile Val MetGlu Asn Arg Asn 260 265 270 Leu His Ser Pro Glu Tyr Leu Glu Met Ala LeuPro Leu Phe Cys Lys 275 280 285 Ala Met Ser Lys Leu Pro Leu Ala Ala GlnGly Lys Leu Ile Arg Leu 290 295 300 Trp Ser Lys Tyr Asn Ala Asp Gln IleArg Arg Met Met Glu Thr Phe 305 310 315 320 Gln Gln Leu Ile Thr Tyr LysVal Ile Ser Asn Glu Phe Asn Ser Arg 325 330 335 Asn Leu Val Asn Asp AspAsp Ala Ile Val Ala Ala Ser Lys Cys Leu 340 345 350 Lys Met Val Tyr TyrAla Asn Val Val Gly Gly Glu Val Asp Thr Asn 355 360 365 His Asn Glu GluAsp Asp Glu Glu Pro Ile Pro Glu Ser Ser Glu Leu 370 375 380 Thr Leu GlnGlu Leu Leu Gly Glu Glu Arg Arg Asn Lys Lys Gly Pro 385 390 395 400 ArgVal Asp Pro Leu Glu Thr Glu Leu Gly Val Lys Thr Leu Asp Cys 405 410 415Arg Lys Pro Leu Ile Pro Phe Glu Glu Phe Ile Asn Glu Pro Leu Asn 420 425430 Glu Val Leu Glu Met Asp Lys Asp Tyr Thr Phe Phe Lys Val Glu Thr 435440 445 Glu Asn Lys Phe Ser Phe Met Thr Cys Pro Phe Ile Leu Asn Ala Val450 455 460 Thr Lys Asn Leu Gly Leu Tyr Tyr Asp Asn Arg Ile Arg Met TyrSer 465 470 475 480 Glu Arg Arg Ile Thr Val Leu Tyr Ser Leu Val Gln GlyGln Gln Leu 485 490 495 Asn Pro Tyr Leu Arg Leu Lys Val Arg Arg Asp HisIle Ile Asp Asp 500 505 510 Ala Leu Val Arg Leu Glu Met Ile Ala Met GluAsn Pro Ala Asp Leu 515 520 525 Lys Lys Gln Leu Tyr Val Glu Phe Glu GlyGlu Gln Gly Val Asp Glu 530 535 540 Gly Gly Val Ser Lys Glu Phe Phe GlnLeu Val Val Glu Glu Ile Phe 545 550 555 560 Asn Pro Asp Ile Gly Met PheThr Tyr Asp Glu Ser Thr Lys Leu Phe 565 570 575 Trp Phe Asn Pro Ser SerPhe Glu Thr Glu Gly Gln Phe Thr Leu Ile 580 585 590 Gly Ile Val Leu GlyLeu Ala Ile Tyr Asn Asn Cys Ile Leu Asp Val 595 600 605 His Phe Pro MetVal Val Tyr Arg Lys Leu Met Gly Lys Lys Gly Thr 610 615 620 Phe Arg AspLeu Gly Asp Ser His Pro Val Leu Tyr Gln Ser Leu Lys 625 630 635 640 AspLeu Leu Glu Tyr Glu Gly Asn Val Glu Asp Asp Met Met Ile Thr 645 650 655Phe Gln Ile Ser Gln Thr Asp Leu Phe Gly Asn Pro Met Met Tyr Asp 660 665670 Leu Lys Glu Asn Gly Asp Lys Ile Pro Ile Thr Asn Glu Asn Arg Lys 675680 685 Glu Phe Val Asn Leu Tyr Ser Asp Tyr Ile Leu Asn Lys Ser Val Glu690 695 700 Lys Gln Phe Lys Ala Phe Arg Arg Gly Phe His Met Val Thr AsnGlu 705 710 715 720 Ser Pro Leu Lys Tyr Leu Phe Arg Pro Glu Glu Ile GluLeu Leu Ile 725 730 735 Cys Gly Ser Arg Asn Leu Asp Phe Gln Ala Leu GluGlu Thr Thr Glu 740 745 750 Tyr Asp Gly Gly Tyr Thr Arg Asp Ser Val LeuIle Arg Glu Phe Trp 755 760 765 Glu Ile Val His Ser Phe Thr Asp Glu GlnLys Arg Leu Phe Leu Gln 770 775 780 Phe Thr Thr Gly Thr Asp Arg Ala ProVal Gly Gly Leu Gly Lys Leu 785 790 795 800 Lys Met Ile Ile Ala Lys AsnGly Pro Asp Thr Glu Arg Leu Pro Thr 805 810 815 Ser His Thr Cys Phe AsnVal Leu Leu Leu Pro Glu Tyr Ser Ser Lys 820 825 830 Glu Lys Leu Lys GluArg Leu Leu Lys Ala Ile Thr Tyr Ala Lys Gly 835 840 845 Phe Gly Met Leu850 26 335 PRT Homo sapiens 26 Met Thr Thr Val Thr Val Thr Thr Glu IlePro Pro Arg Asp Lys Met 1 5 10 15 Glu Asp Asn Ser Ala Leu Tyr Glu SerThr Ser Ala His Ile Ile Glu 20 25 30 Glu Thr Glu Tyr Val Lys Lys Ile ArgThr Thr Leu Gln Lys Ile Arg 35 40 45 Thr Gln Met Phe Lys Asp Glu Ile ArgHis Asp Ser Thr Asn His Lys 50 55 60 Leu Asp Ala Lys His Cys Gly Asn LeuGln Gln Gly Ser Asp Ser Glu 65 70 75 80 Met Asp Pro Ser Cys Cys Ser LeuAsp Leu Leu Met Lys Lys Ile Lys 85 90 95 Gly Lys Asp Leu Gln Leu Leu GluMet Asn Lys Glu Asn Glu Val Leu 100 105 110 Lys Ile Lys Leu Gln Ala SerArg Glu Ala Gly Ala Ala Ala Leu Arg 115 120 125 Asn Val Ala Gln Arg LeuPhe Glu Asn Tyr Gln Thr Gln Ser Glu Glu 130 135 140 Val Arg Lys Lys GlnGlu Asp Ser Lys Gln Leu Leu Gln Val Asn Lys 145 150 155 160 Leu Glu LysGlu Gln Lys Leu Lys Gln His Val Glu Asn Leu Asn Gln 165 170 175 Val AlaGlu Lys Leu Glu Glu Lys His Ser Gln Ile Thr Glu Leu Glu 180 185 190 AsnLeu Val Gln Arg Met Glu Lys Glu Lys Arg Thr Leu Leu Glu Arg 195 200 205Lys Leu Ser Leu Glu Asn Lys Leu Leu Gln Leu Lys Ser Ser Ala Thr 210 215220 Tyr Gly Lys Ser Cys Gln Asp Leu Gln Arg Glu Ile Ser Ile Leu Gln 225230 235 240 Glu Gln Ile Ser His Leu Gln Phe Val Ile His Ser Gln His GlnAsn 245 250 255 Leu Arg Ser Val Ile Gln Glu Met Glu Gly Leu Lys Asn AsnLeu Lys 260 265 270 Glu Gln Asp Lys Arg Ile Glu Asn Leu Arg Glu Lys ValAsn Ile Leu 275 280 285 Glu Ala Gln Asn Lys Glu Leu Lys Thr Gln Val AlaLeu Ser Ser Glu 290 295 300 Thr Pro Arg Thr Lys Val Ser Lys Ala Val SerThr Ser Glu Leu Lys 305 310 315 320 Thr Glu Gly Val Ser Pro Tyr Leu MetLeu Ile Arg Leu Arg Lys 325 330 335 27 254 PRT Homo sapiens 27 Met LeuIle Ser Lys Leu Glu Lys Asn Lys Thr Met Lys Ser Glu Asp 1 5 10 15 LysAla Glu Ile Met Lys Thr Leu Glu Val Leu Thr Lys Asn Ile Thr 20 25 30 LysLeu Lys Asp Glu Val Lys Ala Ala Ser Pro Gly Arg Cys Leu Pro 35 40 45 LysSer Ile Lys Thr Lys Thr Gln Met Gln Lys Glu Leu Leu Asp Thr 50 55 60 GluLeu Asp Leu Tyr Lys Lys Met Gln Ala Gly Glu Glu Val Thr Glu 65 70 75 80Leu Arg Arg Lys Tyr Thr Glu Leu Gln Leu Glu Ala Ala Lys Arg Gly 85 90 95Ile Leu Ser Ser Gly Arg Gly Arg Gly Ile His Ser Arg Gly Arg Gly 100 105110 Ala Val His Gly Arg Gly Arg Gly Arg Gly Arg Gly Arg Gly Val Pro 115120 125 Gly His Ala Val Val Asp His Arg Pro Arg Ala Leu Glu Ile Ser Ala130 135 140 Phe Thr Glu Ser Asp Arg Glu Asp Leu Leu Pro His Phe Ala GlnTyr 145 150 155 160 Gly Glu Ile Glu Asp Cys Gln Ile Asp Asp Ser Ser LeuHis Ala Val 165 170 175 Ile Thr Phe Lys Thr Arg Ala Glu Ala Glu Ala AlaAla Val His Gly 180 185 190 Ala Arg Phe Lys Gly Gln Asp Leu Lys Leu AlaTrp Asn Lys Pro Val 195 200 205 Thr Asn Ile Ser Ala Val Glu Thr Glu GluVal Glu Pro Asp Glu Glu 210 215 220 Glu Phe Gln Glu Glu Ser Leu Val AspAsp Ser Leu Leu Gln Asp Asp 225 230 235 240 Asp Glu Glu Glu Glu Asp AsnGlu Ser Arg Ser Trp Arg Arg 245 250 28 1035 PRT Homo sapiens 28 Met PhePro Tyr Asp Ser Arg Leu Asp Asp Lys Lys Phe Leu Tyr Ser 1 5 10 15 AlaPro Arg Asn Lys Ser His Ile Asp Thr Cys Leu His Ala Tyr Ile 20 25 30 PheArg Pro Glu Val Tyr Gln Leu Pro Ile Cys Lys Leu Lys Glu Leu 35 40 45 PheGlu Glu Asn Arg Lys Leu Gln Gln Phe Ser Pro Leu Ser Asp Tyr 50 55 60 GluGly Gln Glu Glu Glu Met Asn Gly Thr Lys Met Lys Phe Gly Lys 65 70 75 80Arg Asn Asn Ser Arg Gly Glu Ala Ile Ile Ser Gly Lys Gln Arg Ser 85 90 95Ser His Ser Leu Asp Tyr Asp Lys Asp Arg Val Lys Glu Leu Ile Asn 100 105110 Leu Ile Gln Cys Arg Lys Lys Ser Val Gly Gly Asp Ser Asp Thr Glu 115120 125 Asp Met Arg Ser Lys Thr Val Leu Lys Arg Lys Leu Glu Asp Leu Pro130 135 140 Glu Asn Met Arg Lys Leu Ala Lys Thr Ser Asn Leu Ser Glu AsnCys 145 150 155 160 His Leu Tyr Glu Glu Ser Pro Gln Pro Ile Gly Ser LeuGly His Asp 165 170 175 Ala Asp Leu Arg Arg Gln Gln Gln Asp Thr Cys AsnSer Gly Ile Ala 180 185 190 Asp Ile His Arg Leu Phe Asn Trp Leu Ser GluThr Leu Ala Asn Ala 195 200 205 Arg His Ser Asp Ala Ser Leu Thr Asp ThrVal Asn Lys Ala Leu Gly 210 215 220 Leu Ser Thr Asp Asp Ala Tyr Glu GluLeu Arg Gln Lys His Glu Tyr 225 230 235 240 Glu Leu Asn Ser Thr Pro AspLys Lys Asp Tyr Glu Gln Pro Thr Cys 245 250 255 Ala Lys Val Glu Asn AlaGln Phe Lys Gly Thr Gln Ser Leu Leu Leu 260 265 270 Glu Val Asp Ala ThrSer Lys Tyr Ser Val Ala Ile Ser Thr Ser Glu 275 280 285 Val Gly Thr AspHis Lys Leu His Leu Lys Glu Asp Pro Asn Leu Ile 290 295 300 Ser Val AsnAsn Phe Glu Asp Cys Ser Leu Cys Pro Ser Val Pro Ile 305 310 315 320 GluHis Gly Phe Arg Arg Gln Gln Ser Lys Ser Asn Asn Val Glu Glu 325 330 335Thr Glu Ile His Trp Lys Leu Ile Pro Ile Thr Asp Thr Leu Lys Gly 340 345350 Thr Thr Glu Asp Asp Val Leu Thr Gly Gln Val Glu Glu Gln Cys Val 355360 365 Pro Ala Ala Glu Ala Glu Pro Pro Ala Val Ser Glu Thr Thr Glu Arg370 375 380 Thr Val Leu Gly Glu Tyr Asn Leu Phe Ser Arg Lys Ile Glu GluIle 385 390 395 400 Leu Lys Gln Lys Asn Val Ser Tyr Val Ser Arg Val SerThr Pro Ile 405 410 415 Phe Ser Thr Gln Glu Lys Met Lys Arg Leu Ser GluPhe Ile Tyr Ser 420 425 430 Lys Thr Ser Lys Ala Gly Val Gln Glu Phe ValAsp Gly Leu His Glu 435 440 445 Lys Leu Asn Thr Ile Ile Ile Lys Ala SerAla Lys Gly Gly Asn Leu 450 455 460 Pro Pro Val Ser Pro Asn Asp Ser GlyAla Lys Ile Ala Ser Asn Pro 465 470 475 480 Leu Glu Arg His Val Ile ProVal Ser Ser Ser Asp Phe Asn Asn Lys 485 490 495 His Leu Leu Glu Pro LeuCys Ser Asp Pro Leu Lys Asp Thr Asn Ser 500 505 510 Asp Glu Gln His SerThr Ser Ala Leu Thr Glu Val Glu Met Asn Gln 515 520 525 Pro Gln His AlaThr Glu Leu Met Val Thr Ser Asp His Ile Val Pro 530 535 540 Gly Asp MetAla Arg Glu Pro Val Glu Glu Thr Thr Lys Ser Pro Ser 545 550 555 560 AspVal Asn Ile Ser Ala Gln Pro Ala Leu Ser Asn Phe Ile Ser Gln 565 570 575Leu Glu Pro Glu Val Phe Asn Ser Leu Val Lys Ile Met Lys Asp Val 580 585590 Gln Lys Asn Thr Val Lys Phe Tyr Ile His Glu Glu Glu Glu Ser Val 595600 605 Leu Cys Lys Glu Ile Lys Glu Tyr Leu Ile Lys Leu Gly Asn Thr Glu610 615 620 Cys His Pro Glu Gln Phe Leu Glu Arg Arg Ser Lys Leu Asp LysLeu 625 630 635 640 Leu Ile Ile Ile Gln Asn Glu Asp Ile Ala Gly Phe IleHis Lys Ile 645 650 655 Pro Gly Leu Val Thr Leu Lys Lys Leu Pro Cys ValSer Phe Ala Gly 660 665 670 Val Asp Ser Leu Asp Asp Val Lys Asn His ThrTyr Asn Glu Leu Phe 675 680 685 Val Ser Gly Gly Phe Ile Val Ser Asp GluSer Ile Leu Asn Pro Glu 690 695 700 Val Val Thr Val Glu Asn Leu Lys AsnPhe Leu Thr Phe Leu Glu Glu 705 710 715 720 Leu Ser Thr Pro Glu Gly LysTrp Gln Trp Lys Val His Cys Lys Phe 725 730 735 Gln Lys Lys Leu Lys GluLeu Gly Arg Leu Asn Ala Lys Ala Leu Ser 740 745 750 Leu Leu Thr Leu LeuAsn Val Tyr Gln Lys Lys His Leu Val Glu Ile 755 760 765 Leu Ser Tyr HisAsn Cys Asp Ser Gln Thr Arg Asn Ala Pro Glu Leu 770 775 780 Asp Cys LeuIle Arg Leu Gln Ala Gln Asn Ile Gln Gln Arg His Val 785 790 795 800 ValPhe Leu Thr Glu Lys Asn Ile Lys Met Leu Ser Ser Tyr Thr Asp 805 810 815Asn Gly Ile Val Val Ala Thr Ala Glu Asp Phe Met Gln Asn Phe Lys 820 825830 Asn Leu Val Gly Tyr His Asn Ser Ile Thr Glu Glu Asn Leu Pro Gln 835840 845 Leu Gly Ala Asn Glu Asn Leu Glu Ser Gln Ser Ala Leu Leu Glu Asn850 855 860 Asp Glu Lys Asp Glu Glu Asp Met Ser Leu Asp Ser Gly Asp GluIle 865 870 875 880 Ser His Ile Glu Val Cys Ser Asn Phe His Ser Glu IleTrp Glu Lys 885 890 895 Glu Thr Lys Gly Ser Arg Gly Thr Asp Gln Lys LysAsn Thr Gln Ile 900 905 910 Glu Leu Gln Ser Ser Pro Asp Val Gln Asn SerLeu Leu Glu Asp Lys 915 920 925 Thr Tyr Leu Asp Ser Glu Glu Arg Thr SerIle Asp Ile Val Cys Ser 930 935 940 Glu Gly Glu Asn Ser Asn Ser Thr GluGln Asp Ser Tyr Ser Asn Phe 945 950 955 960 Gln Val Tyr His Ser Gln LeuAsn Met Ser His Gln Phe Ser His Phe 965 970 975 Asn Val Leu Thr His GlnThr Phe Leu Gly Thr Pro Tyr Ala Leu Ser 980 985 990 Ser Ser Gln Ser GlnGlu Asn Glu Asn Tyr Phe Leu Ser Ala Tyr Thr 995 1000 1005 Glu Ser LeuAsp Arg Asp Lys Ser Pro Pro Pro Leu Ser Trp Gly Lys 1010 1015 1020 SerAsp Ser Ser Arg Pro Tyr Ser Gln Glu Lys 1025 1030 1035 29 613 PRT Homosapiens 29 Met Asn Lys Gly Glu His Ala Leu Val Leu Phe Glu Lys Cys ValGln 1 5 10 15 Asp Lys Tyr Leu Gln Gln Glu His Ile Ile Lys Lys Leu IleLys Glu 20 25 30 Asn Lys Lys His Gln Glu Leu Phe Val Asp Ile Cys Ser GluLys Asp 35 40 45 Asn Leu Arg Glu Glu Leu Lys Lys Arg Thr Glu Thr Glu LysGln His 50 55 60 Met Asn Thr Ile Lys Gln Leu Glu Ser Arg Ile Glu Glu LeuAsn Lys 65 70 75 80 Glu Val Lys Ala Ser Arg Asp Lys Leu Ile Ala Gln AspVal Thr Ala 85 90 95 Lys Asn Ala Val Gln Gln Leu His Lys Glu Met Ala GlnArg Met Glu 100 105 110 Gln Ala Asn Lys Lys Cys Glu Glu Ala Arg Gln GluLys Glu Ala Met 115 120 125 Val Met Lys Tyr Val Arg Gly Glu Lys Glu SerLeu Asp Leu Arg Lys 130 135 140 Glu Lys Glu Thr Leu Glu Lys Lys Leu ArgAsp Ala Asn Lys Glu Leu 145 150 155 160 Glu Lys Asn Thr Asn Lys Ile LysGln Leu Ser Gln Glu Lys Gly Arg 165 170 175 Leu His Gln Leu Tyr Glu ThrLys Glu Gly Glu Thr Thr Arg Leu Ile 180 185 190 Arg Glu Ile Asp Lys LeuLys Glu Asp Ile Asn Ser His Val Ile Lys 195 200 205 Val Lys Trp Ala GlnAsn Lys Leu Lys Ala Glu Met Asp Ser His Lys 210 215 220 Glu Thr Lys AspLys Leu Lys Glu Thr Thr Thr Lys Leu Thr Gln Ala 225 230 235 240 Lys GluGlu Ala Asp Gln Ile Arg Lys Asn Cys Gln Asp Met Ile Lys 245 250 255 ThrTyr Gln Glu Ser Glu Glu Ile Lys Ser Asn Glu Leu Asp Ala Lys 260 265 270Leu Arg Val Thr Lys Gly Glu Leu Glu Lys Gln Met Gln Glu Lys Ser 275 280285 Asp Gln Leu Glu Met His His Ala Lys Ile Lys Glu Leu Glu Asp Leu 290295 300 Lys Arg Thr Phe Lys Glu Gly Met Asp Glu Leu Arg Thr Leu Arg Thr305 310 315 320 Lys Val Lys Cys Leu Glu Asp Glu Arg Leu Arg Thr Glu AspGlu Leu 325 330 335 Ser Lys Tyr Lys Glu Ile Ile Asn Arg Gln Lys Ala GluIle Gln Asn 340 345 350 Leu Leu Asp Lys Val Lys Thr Ala Asp Gln Leu GlnGlu Gln Leu Gln 355 360 365 Arg Gly Lys Gln Glu Ile Glu Asn Leu Lys GluGlu Val Glu Ser Leu 370 375 380 Asn Ser Leu Ile Asn Asp Leu Gln Lys AspIle Glu Gly Ser Arg Lys 385 390 395 400 Arg Glu Ser Glu Leu Leu Leu PheThr Glu Arg Leu Thr Ser Lys Asn 405 410 415 Ala Gln Leu Gln Ser Glu SerAsn Ser Leu Gln Ser Gln Phe Asp Lys 420 425 430 Val Ser Cys Ser Glu SerGln Leu Gln Ser Gln Cys Glu Gln Met Lys 435 440 445 Gln Thr Asn Ile AsnLeu Glu Ser Arg Leu Leu Lys Glu Glu Glu Leu 450 455 460 Arg Lys Glu GluVal Gln Thr Leu Gln Ala Glu Leu Ala Cys Arg Gln 465 470 475 480 Thr GluVal Lys Ala Leu Ser Thr Gln Val Glu Glu Leu Lys Asp Glu 485 490 495 LeuVal Thr Gln Arg Arg Lys His Ala Ser Ser Ile Lys Asp Leu Thr 500 505 510Lys Gln Leu Gln Gln Ala Arg Arg Lys Leu Asp Gln Val Glu Ser Gly 515 520525 Ser Tyr Asp Lys Glu Val Ser Ser Met Gly Ser Arg Ser Ser Ser Ser 530535 540 Gly Ser Leu Asn Ala Arg Ser Ser Ala Glu Asp Arg Ser Pro Glu Asn545 550 555 560 Thr Gly Ser Ser Val Ala Val Asp Asn Phe Pro Gln Val AspLys Ala 565 570 575 Met Leu Ile Glu Arg Ile Val Arg Leu Gln Lys Ala HisAla Arg Lys 580 585 590 Asn Glu Lys Ile Glu Phe Met Glu Asp His Ile LysGln Leu Val Glu 595 600 605 Lys Lys Lys Lys Lys 610 30 810 PRT Homosapiens 30 Met Ser Lys Lys Gly Arg Asn Lys Gly Glu Lys Pro Glu Ala LeuIle 1 5 10 15 Val Ala Leu Gln Ala Ala Asn Glu Asp Leu Arg Thr Lys LeuThr Asp 20 25 30 Ile Gln Ile Glu Leu His Gln Glu Lys Ser Lys Val Ser LysLeu Glu 35 40 45 Arg Glu Lys Thr Gln Glu Ala Lys Arg Ile Arg Glu Leu GluGln Arg 50 55 60 Lys His Thr Val Leu Val Thr Glu Leu Lys Ala Lys Leu HisGlu Glu 65 70 75 80 Lys Met Lys Glu Leu Gln Ala Val Arg Glu Asn Leu IleLys Gln His 85 90 95 Glu Gln Glu Met Ser Arg Thr Val Lys Val Arg Asp GlyGlu Ile Gln 100 105 110 Arg Leu Lys Ser Ala Leu Cys Ala Leu Arg Asp GlySer Ser Asp Lys 115 120 125 Val Arg Thr Ala Leu Thr Ile Glu Ala Arg GluGlu Ala Arg Lys Leu 130 135 140 Phe Asp Thr Glu Arg Leu Lys Leu Leu GlnGlu Ile Ala Asp Leu Lys 145 150 155 160 Thr Ala Lys Lys Gln Val Asp GluAla Leu Ser Asn Met Ile Gln Ala 165 170 175 Asp Lys Ile Lys Ala Gly AspLeu Arg Ser Glu His Gln Ser His Gln 180 185 190 Glu Ala Ile Ser Lys IleLys Trp Glu Ser Glu Arg Asp Ile Arg Arg 195 200 205 Leu Met Asp Glu IleLys Ala Lys Asp Arg Ile Ile Phe Ser Leu Glu 210 215 220 Lys Glu Leu GluThr Gln Thr Gly Tyr Val Gln Lys Leu Gln Leu Gln 225 230 235 240 Lys GluAla Leu Asp Glu Gln Leu Phe Leu Val Lys Glu Ala Glu Cys 245 250 255 AsnMet Ser Ser Pro Lys Arg Glu Ile Pro Gly Arg Ala Gly Asp Gly 260 265 270Ser Glu His Cys Ser Ser Pro Asp Leu Arg Arg Asn Gln Lys Arg Ile 275 280285 Ala Glu Leu Asn Ala Thr Ile Arg Lys Leu Glu Asp Arg Asn Thr Leu 290295 300 Leu Gly Asp Glu Arg Asn Glu Leu Leu Lys Arg Val Arg Glu Thr Glu305 310 315 320 Lys Gln Cys Lys Pro Leu Leu Glu Arg Asn Lys Cys Leu AlaLys Arg 325 330 335 Asn Asp Glu Leu Met Val Ser Leu Gln Arg Met Glu GluLys Leu Lys 340 345 350 Ala Val Thr Lys Glu Asn Ser Glu Met Arg Glu LysIle Thr Ser His 355 360 365 Pro Pro Leu Lys Lys Leu Lys Ser Leu Asn AspLeu Asp Gln Ala Asn 370 375 380 Glu Glu Gln Glu Thr Glu Phe Leu Lys LeuGln Val Ile Glu Gln Gln 385 390 395 400 Asn Ile Ile Asp Glu Leu Thr ArgAsp Arg Glu Lys Leu Ile Arg Arg 405 410 415 Arg Lys His Arg Arg Ser SerLys Pro Ile Lys Arg Pro Val Leu Asp 420 425 430 Pro Phe Ile Gly Tyr AspGlu Asp Ser Met Asp Ser Glu Thr Ser Ser 435 440 445 Met Ala Ser Phe ArgThr Asp Arg Thr Pro Ala Thr Pro Asp Asp Asp 450 455 460 Leu Asp Glu SerLeu Ala Ala Glu Glu Ser Glu Leu Arg Phe Arg Gln 465 470 475 480 Leu ThrLys Glu Tyr Gln Ala Leu Gln Arg Ala Tyr Ala Leu Leu Gln 485 490 495 GluGln Thr Gly Gly Ile Ile Asp Ala Glu Arg Glu Ala Lys Ala Gln 500 505 510Glu Gln Leu Gln Ala Glu Val Leu Arg Tyr Lys Ala Lys Ile Glu Asp 515 520525 Leu Glu Ala Thr Leu Ala Gln Lys Gly Gln Asp Ser His Trp Val Glu 530535 540 Asp Lys Gln Leu Phe Ile Lys Arg Asn Gln Glu Leu Leu Glu Lys Ile545 550 555 560 Glu Lys Gln Glu Ala Glu Asn His Arg Leu Gln Gln Glu LeuGln Asp 565 570 575 Ala Arg Asp Gln Asn Glu Leu Leu Glu Phe Arg Asn LeuGlu Leu Glu 580 585 590 Glu Arg Glu Arg Arg Ser Pro Pro Phe Asn Leu GlnIle His Pro Phe 595 600 605 Ser Asp Gly Val Ser Ala Leu Gln Ile Tyr CysMet Lys Glu Gly Val 610 615 620 Lys Asp Val Asn Ile Pro Asp Leu Ile LysGln Leu Asp Ile Leu Gly 625 630 635 640 Asp Asn Gly Asn Leu Arg Asn GluGlu Gln Val Ala Ile Ile Gln Ala 645 650 655 Ser Thr Val Leu Ser Leu AlaGlu Lys Trp Ile Gln Gln Ile Glu Gly 660 665 670 Ala Glu Ala Ala Leu HisGln Lys Met Met Glu Leu Glu Ser Asp Met 675 680 685 Glu Gln Phe Cys LysIle Lys Gly Tyr Leu Glu Glu Glu Leu Asp Tyr 690 695 700 Arg Lys Gln AlaLeu Asp Gln Ala Tyr Met Arg Ile Gln Glu Leu Glu 705 710 715 720 Ala ThrLeu Tyr Asn Ala Leu Gln Gln Glu Thr Val Ile Lys Phe Gly 725 730 735 GluLeu Leu Ser Glu Lys Gln Gln Glu Glu Leu Arg Thr Ala Val Glu 740 745 750Lys Leu Arg Arg Gln Met Leu Arg Lys Ser Arg Glu Tyr Asp Cys Gln 755 760765 Ile Leu Gln Glu Arg Met Glu Leu Leu Gln Gln Ala His Gln Arg Ile 770775 780 Arg Asp Leu Glu Asp Lys Thr Asp Ile Gln Lys Arg Gln Ile Lys Asp785 790 795 800 Leu Glu Glu Lys Ser Asn Arg Lys His Gly 805 810 31 387PRT Homo sapiens 31 Met Ala Gly Lys Ala Ala Ala Pro Gly Thr Ala Val LeuLeu Val Thr 1 5 10 15 Ala Asn Val Gly Ser Leu Phe Asp Asp Pro Glu AsnLeu Gln Lys Asn 20 25 30 Trp Leu Arg Glu Phe Tyr Gln Val Val His Thr HisArg Pro His Phe 35 40 45 Met Ala Leu His Cys Gln Glu Phe Gly Gly Lys AsnTyr Glu Ala Ser 50 55 60 Met Ser His Val Asp Lys Phe Val Lys Glu Leu LeuSer Ser Asp Ala 65 70 75 80 Met Lys Glu Tyr Asn Arg Ala Arg Val Tyr LeuAsp Glu Asn Tyr Lys 85 90 95 Ser Gln Glu His Phe Thr Ala Leu Gly Ser PheTyr Phe Leu His Glu 100 105 110 Ser Leu Lys Asn Ile Tyr Gln Phe Asp PheLys Ala Lys Lys Tyr Arg 115 120 125 Lys Val Ala Gly Lys Glu Ile Tyr SerAsp Thr Leu Glu Ser Thr Pro 130 135 140 Met Leu Glu Lys Glu Lys Phe ProGln Asp Tyr Phe Pro Glu Cys Lys 145 150 155 160 Trp Ser Arg Lys Gly PheIle Arg Thr Arg Trp Cys Ile Ala Asp Cys 165 170 175 Ala Phe Asp Leu ValAsn Ile His Leu Phe His Asp Ala Ser Asn Leu 180 185 190 Val Ala Trp GluThr Ser Pro Ser Val Tyr Ser Gly Ile Arg His Lys 195 200 205 Ala Leu GlyTyr Val Leu Asp Arg Ile Ile Asp Gln Arg Phe Glu Lys 210 215 220 Val SerTyr Phe Val Phe Gly Asp Phe Asn Phe Arg Leu Asp Ser Lys 225 230 235 240Ser Val Val Glu Thr Leu Cys Thr Lys Ala Thr Met Gln Thr Val Arg 245 250255 Ala Ala Asp Thr Asn Glu Val Val Lys Leu Ile Phe Arg Glu Ser Asp 260265 270 Asn Asp Arg Lys Val Met Leu Gln Leu Glu Lys Lys Leu Phe Asp Tyr275 280 285 Phe Asn Gln Glu Val Phe Arg Asp Asn Asn Gly Thr Ala Leu LeuGlu 290 295 300 Phe Asp Lys Glu Leu Ser Val Phe Lys Asp Arg Leu Tyr GluLeu Asp 305 310 315 320 Ile Ser Phe Pro Pro Ser Tyr Pro Tyr Ser Glu AspAla Arg Gln Gly 325 330 335 Glu Gln Tyr Met Asn Thr Arg Cys Pro Ala TrpCys Asp Arg Ile Leu 340 345 350 Met Ser Pro Ser Ala Lys Glu Leu Val LeuArg Val Ser Val Cys Cys 355 360 365 Pro Ser Pro Gly His Arg Gly Met TrpSer Ala Gly Ser Gly Leu Ala 370 375 380 Gln Pro Trp 385 32 300 PRT Homosapiens 32 Met Lys Phe Leu Leu Asp Ile Leu Leu Leu Leu Pro Leu Leu IleVal 1 5 10 15 Cys Ser Leu Glu Ser Phe Val Lys Leu Phe Ile Pro Lys ArgArg Lys 20 25 30 Ser Val Thr Gly Glu Ile Val Leu Ile Thr Gly Ala Gly HisGly Ile 35 40 45 Gly Arg Leu Thr Ala Tyr Glu Phe Ala Lys Leu Lys Ser LysLeu Val 50 55 60 Leu Trp Asp Ile Asn Lys His Gly Leu Glu Glu Thr Ala AlaLys Cys 65 70 75 80 Lys Gly Leu Gly Ala Lys Val His Thr Phe Val Val AspCys Ser Asn 85 90 95 Arg Glu Asp Ile Tyr Ser Ser Ala Lys Lys Val Lys AlaGlu Ile Gly 100 105 110 Asp Val Ser Ile Leu Val Asn Asn Ala Gly Val ValTyr Thr Ser Asp 115 120 125 Leu Phe Ala Thr Gln Asp Pro Gln Ile Glu LysThr Phe Glu Val Asn 130 135 140 Val Leu Ala His Phe Trp Thr Thr Lys AlaPhe Leu Pro Ala Met Thr 145 150 155 160 Lys Asn Asn His Gly His Ile ValThr Val Ala Ser Ala Ala Gly His 165 170 175 Val Ser Val Pro Phe Leu LeuAla Tyr Cys Ser Ser Lys Phe Ala Ala 180 185 190 Val Gly Phe His Lys ThrLeu Thr Asp Glu Leu Ala Ala Leu Gln Ile 195 200 205 Thr Gly Val Lys ThrThr Cys Leu Cys Pro Asn Phe Val Asn Thr Gly 210 215 220 Phe Ile Lys AsnPro Ser Thr Ser Leu Gly Pro Thr Leu Glu Pro Glu 225 230 235 240 Glu ValVal Asn Arg Leu Met His Gly Ile Leu Thr Glu Gln Lys Met 245 250 255 IlePhe Ile Pro Ser Ser Ile Ala Phe Leu Thr Thr Leu Glu Arg Ile 260 265 270Leu Pro Glu Arg Phe Leu Ala Val Leu Lys Arg Lys Ile Ser Val Lys 275 280285 Phe Asp Ala Val Ile Gly Tyr Lys Met Lys Ala Gln 290 295 300 33 361PRT Homo sapiens 33 Met Ile Thr Gly Thr Ser Gln Ala Asp Cys Ala Val LeuIle Val Ala 1 5 10 15 Ala Gly Val Gly Glu Phe Glu Ala Gly Ile Ser LysAsn Gly Gln Thr 20 25 30 Arg Glu His Ala Leu Leu Ala Tyr Thr Leu Gly ValLys Gln Leu Ile 35 40 45 Val Gly Val Asn Lys Met Asp Ser Thr Glu Pro ProTyr Ser Gln Lys 50 55 60 Arg Tyr Glu Glu Ile Val Lys Glu Val Ser Thr TyrIle Lys Lys Ile 65 70 75 80 Gly Tyr Asn Pro Asp Thr Val Ala Phe Val ProIle Ser Gly Trp Asn 85 90 95 Gly Asp Asn Met Leu Glu Pro Ser Ala Asn MetPro Trp Phe Lys Gly 100 105 110 Trp Lys Val Thr Arg Lys Asp Gly Asn AlaSer Gly Thr Thr Leu Leu 115 120 125 Glu Ala Leu Asp Cys Ile Leu Pro ProThr Arg Pro Thr Asp Lys Pro 130 135 140 Leu Arg Leu Pro Leu Gln Asp ValTyr Lys Ile Gly Gly Ile Gly Thr 145 150 155 160 Val Pro Val Gly Arg ValGlu Thr Gly Val Leu Lys Pro Gly Met Val 165 170 175 Val Thr Phe Ala ProVal Asn Val Thr Thr Glu Val Lys Ser Val Glu 180 185 190 Met His His GluAla Leu Ser Glu Ala Leu Pro Gly Asp Asn Val Gly 195 200 205 Phe Asn ValLys Asn Val Ser Val Lys Asp Val Arg Arg Gly Asn Val 210 215 220 Ala GlyAsp Ser Lys Asn Asp Pro Pro Met Glu Ala Ala Gly Phe Thr 225 230 235 240Ala Gln Val Ile Ile Leu Asn His Pro Gly Gln Ile Ser Ala Gly Tyr 245 250255 Ala Pro Val Leu Asp Cys His Thr Ala His Ile Ala Cys Lys Phe Ala 260265 270 Glu Leu Lys Glu Lys Ile Asp Arg Arg Ser Gly Lys Lys Leu Glu Asp275 280 285 Gly Pro Lys Phe Leu Lys Ser Gly Asp Ala Ala Ile Val Asp MetVal 290 295 300 Pro Gly Lys Pro Met Cys Val Glu Ser Phe Ser Asp Tyr ProPro Leu 305 310 315 320 Gly Arg Phe Ala Val Arg Asp Met Arg Gln Thr ValAla Val Gly Val 325 330 335 Ile Lys Ala Val Asp Lys Lys Ala Ala Gly AlaGly Lys Val Thr Lys 340 345 350 Ser Ala Gln Lys Ala Gln Lys Ala Lys 355360 34 795 PRT Homo sapiens 34 Met Glu Lys Gln Lys Pro Phe Ala Leu PheVal Pro Pro Arg Ser Ser 1 5 10 15 Ser Ser Gln Val Ser Ala Val Lys ProGln Thr Leu Gly Gly Asp Ser 20 25 30 Thr Phe Phe Lys Ser Phe Asn Lys CysThr Glu Asp Asp Phe Glu Phe 35 40 45 Pro Phe Ala Lys Thr Asn Leu Ser LysAsn Gly Glu Asn Ile Asp Ser 50 55 60 Asp Pro Ala Leu Gln Lys Val Asn PheLeu Pro Val Leu Glu Gln Val 65 70 75 80 Gly Asn Ser Asp Cys His Tyr GlnGlu Gly Leu Lys Asp Ser Asp Leu 85 90 95 Glu Asn Ser Glu Gly Leu Ser ArgVal Tyr Ser Lys Leu Tyr Lys Glu 100 105 110 Ala Glu Lys Ile Lys Lys TrpLys Val Ser Thr Glu Ala Glu Leu Arg 115 120 125 Gln Lys Glu Ser Lys LeuGln Glu Asn Arg Lys Ile Ile Glu Ala Gln 130 135 140 Arg Lys Ala Ile GlnGlu Leu Gln Phe Gly Asn Glu Lys Val Ser Leu 145 150 155 160 Lys Leu GluGlu Gly Ile Gln Glu Asn Lys Asp Leu Ile Lys Glu Asn 165 170 175 Asn AlaThr Arg His Leu Cys Asn Leu Leu Lys Glu Thr Cys Ala Arg 180 185 190 SerAla Glu Lys Thr Lys Lys Tyr Glu Tyr Glu Arg Glu Glu Thr Arg 195 200 205Gln Val Tyr Met Asp Leu Asn Asn Asn Ile Glu Lys Met Ile Thr Ala 210 215220 Phe Glu Glu Leu Arg Val Gln Ala Glu Asn Ser Arg Leu Glu Met His 225230 235 240 Phe Lys Leu Lys Glu Asp Tyr Glu Lys Ile Gln His Leu Glu GlnGlu 245 250 255 Tyr Lys Lys Glu Ile Asn Asp Lys Glu Lys Gln Val Ser LeuLeu Leu 260 265 270 Ile Gln Ile Thr Glu Lys Glu Asn Lys Met Lys Asp LeuThr Phe Leu 275 280 285 Leu Glu Glu Ser Arg Asp Lys Val Asn Gln Leu GluGlu Lys Thr Lys 290 295 300 Leu Gln Ser Glu Asn Leu Lys Gln Ser Ile GluLys Gln His His Leu 305 310 315 320 Thr Lys Glu Leu Glu Asp Ile Lys ValSer Leu Gln Arg Ser Val Ser 325 330 335 Thr Gln Lys Ala Leu Glu Glu AspLeu Gln Ile Ala Thr Lys Thr Ile 340 345 350 Cys Gln Leu Thr Glu Glu LysGlu Thr Gln Met Glu Glu Ser Asn Lys 355 360 365 Ala Arg Ala Ala His SerPhe Val Val Thr Glu Phe Glu Thr Thr Val 370 375 380 Cys Ser Leu Glu GluLeu Leu Arg Thr Glu Gln Gln Arg Leu Glu Lys 385 390 395 400 Asn Glu AspGln Leu Lys Ile Leu Thr Met Glu Leu Gln Lys Lys Ser 405 410 415 Ser GluLeu Glu Glu Met Thr Lys Leu Thr Asn Asn Lys Glu Val Glu 420 425 430 LeuGlu Glu Leu Lys Lys Val Leu Gly Glu Lys Glu Thr Leu Leu Tyr 435 440 445Glu Asn Lys Gln Phe Glu Lys Ile Ala Glu Glu Leu Lys Gly Thr Glu 450 455460 Gln Glu Leu Ile Gly Leu Leu Gln Ala Arg Glu Lys Glu Val His Asp 465470 475 480 Leu Glu Ile Gln Leu Thr Ala Ile Thr Thr Ser Glu Gln Tyr TyrSer 485 490 495 Lys Glu Val Lys Asp Leu Lys Thr Glu Leu Glu Asn Glu LysLeu Lys 500 505 510 Asn Thr Glu Leu Thr Ser His Cys Asn Lys Leu Ser LeuGlu Asn Lys 515 520 525 Glu Leu Thr Gln Glu Thr Ser Asp Met Thr Leu GluLeu Lys Asn Gln 530 535 540 Gln Glu Asp Ile Asn Asn Asn Lys Lys Gln GluGlu Arg Met Leu Lys 545 550 555 560 Gln Ile Glu Asn Leu Gln Glu Thr GluThr Gln Leu Arg Asn Glu Leu 565 570 575 Glu Tyr Val Arg Glu Glu Leu LysGln Lys Arg Asp Glu Val Lys Cys 580 585 590 Lys Leu Asp Lys Ser Glu GluAsn Cys Asn Asn Leu Arg Lys Gln Val 595 600 605 Glu Asn Lys Asn Lys TyrIle Glu Glu Leu Gln Gln Glu Asn Lys Ala 610 615 620 Leu Lys Lys Lys GlyThr Ala Glu Ser Lys Gln Leu Asn Val Tyr Glu 625 630 635 640 Ile Lys ValAsn Lys Leu Glu Leu Glu Leu Glu Ser Ala Lys Gln Lys 645 650 655 Phe GlyGlu Ile Thr Asp Thr Tyr Gln Lys Glu Ile Glu Asp Lys Lys 660 665 670 IleSer Glu Glu Asn Leu Leu Glu Glu Val Glu Lys Ala Lys Val Ile 675 680 685Ala Asp Glu Ala Val Lys Leu Gln Lys Glu Ile Asp Lys Arg Cys Gln 690 695700 His Lys Ile Ala Glu Met Val Ala Leu Met Glu Lys His Lys His Gln 705710 715 720 Tyr Asp Lys Ile Ile Glu Glu Arg Asp Ser Glu Leu Gly Leu TyrLys 725 730 735 Ser Lys Glu Gln Glu Gln Ser Ser Leu Arg Ala Ser Leu GluIle Glu 740 745 750 Leu Ser Asn Leu Lys Ala Glu Leu Leu Ser Val Lys LysGln Leu Glu 755 760 765 Ile Glu Arg Glu Glu Lys Glu Lys Leu Lys Arg GluAla Lys Glu Asn 770 775 780 Thr Ala Thr Leu Lys Glu Lys Lys Lys Lys Lys785 790 795 35 761 PRT Homo sapiens 35 Met Glu Gln Thr Val Ala Glu GlnAsp Asp Ser Leu Ser Ser Leu Leu 1 5 10 15 Val Lys Leu Lys Lys Val SerGln Asp Leu Glu Arg Gln Arg Glu Ile 20 25 30 Thr Glu Leu Lys Val Lys GluPhe Glu Asn Ile Lys Leu Gln Leu Gln 35 40 45 Glu Asn His Glu Asp Glu ValLys Lys Val Lys Ala Glu Val Glu Asp 50 55 60 Leu Lys Tyr Leu Leu Asp GlnSer Gln Lys Glu Ser Gln Cys Leu Lys 65 70 75 80 Ser Glu Leu Gln Ala GlnLys Glu Ala Asn Ser Arg Ala Pro Thr Thr 85 90 95 Thr Met Arg Asn Leu ValGlu Arg Leu Lys Ser Gln Leu Ala Leu Lys 100 105 110 Glu Lys Gln Gln LysAla Leu Ser Arg Ala Leu Leu Glu Leu Arg Ala 115 120 125 Glu Met Thr AlaAla Ala Glu Glu Arg Ile Ile Ser Ala Thr Ser Gln 130 135 140 Lys Glu AlaHis Leu Asn Val Gln Gln Ile Val Asp Arg His Thr Arg 145 150 155 160 GluLeu Lys Thr Gln Val Glu Asp Leu Asn Glu Asn Leu Leu Lys Leu 165 170 175Lys Glu Ala Leu Lys Thr Ser Lys Asn Arg Glu Asn Ser Leu Thr Asp 180 185190 Asn Leu Asn Asp Leu Asn Asn Glu Leu Gln Lys Lys Gln Lys Ala Tyr 195200 205 Asn Lys Ile Leu Arg Glu Lys Glu Glu Ile Asp Gln Glu Asn Asp Glu210 215 220 Leu Lys Arg Gln Ile Lys Arg Leu Thr Ser Gly Leu Gln Gly LysPro 225 230 235 240 Leu Thr Asp Asn Lys Gln Ser Leu Ile Glu Glu Leu GlnArg Lys Val 245 250 255 Lys Lys Leu Glu Asn Gln Leu Glu Gly Lys Val GluGlu Val Asp Leu 260 265 270 Lys Pro Met Lys Glu Lys Asn Ala Lys Glu GluLeu Ile Arg Trp Glu 275 280 285 Glu Gly Lys Lys Trp Gln Ala Lys Ile GluGly Ile Arg Asn Lys Leu 290 295 300 Lys Glu Lys Glu Gly Glu Val Phe ThrLeu Thr Lys Gln Leu Asn Thr 305 310 315 320 Leu Lys Asp Leu Phe Ala LysAla Asp Lys Glu Lys Leu Thr Leu Gln 325 330 335 Arg Lys Leu Lys Thr ThrGly Met Thr Val Asp Gln Val Leu Gly Ile 340 345 350 Arg Ala Leu Glu SerGlu Lys Glu Leu Glu Glu Leu Lys Lys Arg Asn 355 360 365 Leu Asp Leu GluAsn Asp Ile Leu Tyr Met Arg Ala His Gln Ala Leu 370 375 380 Pro Arg AspSer Val Val Glu Asp Leu His Leu Gln Asn Arg Tyr Leu 385 390 395 400 GlnGlu Lys Leu His Ala Leu Glu Lys Gln Phe Ser Lys Asp Thr Tyr 405 410 415Ser Lys Pro Ser Ile Ser Gly Ile Glu Ser Asp Asp His Cys Gln Arg 420 425430 Glu Gln Glu Leu Gln Lys Glu Asn Leu Lys Leu Ser Ser Glu Asn Ile 435440 445 Glu Leu Lys Phe Gln Leu Glu Gln Ala Asn Lys Asp Leu Pro Arg Leu450 455 460 Lys Asn Gln Val Arg Asp Leu Lys Glu Met Cys Glu Phe Leu LysLys 465 470 475 480 Glu Lys Ala Glu Val Gln Arg Lys Leu Gly His Val ArgGly Ser Gly 485 490 495 Arg Ser Gly Lys Thr Ile Pro Glu Leu Glu Lys ThrIle Gly Leu Met 500 505 510 Lys Lys Val Val Glu Lys Val Gln Arg Glu AsnGlu Gln Leu Lys Lys 515 520 525 Ala Ser Gly Ile Leu Thr Ser Glu Lys MetAla Asn Ile Glu Gln Glu 530 535 540 Asn Glu Lys Leu Lys Ala Glu Leu GluLys Leu Lys Ala His Leu Gly 545 550 555 560 His Gln Leu Ser Met His TyrGlu Ser Lys Thr Lys Gly Thr Glu Lys 565 570 575 Ile Ile Ala Glu Asn GluArg Leu Arg Lys Glu Leu Lys Lys Glu Thr 580 585 590 Asp Ala Ala Glu LysLeu Arg Ile Ala Lys Asn Asn Leu Glu Ile Leu 595 600 605 Asn Glu Lys MetThr Val Gln Leu Glu Glu Thr Gly Lys Arg Leu Gln 610 615 620 Phe Ala GluSer Arg Gly Pro Gln Leu Glu Gly Ala Asp Ser Lys Ser 625 630 635 640 TrpLys Ser Ile Val Val Thr Arg Met Tyr Glu Thr Lys Leu Lys Glu 645 650 655Leu Glu Thr Asp Ile Ala Lys Lys Asn Gln Ser Ile Thr Asp Leu Lys 660 665670 Gln Leu Val Lys Glu Ala Thr Glu Arg Glu Gln Lys Val Asn Lys Tyr 675680 685 Asn Glu Asp Leu Glu Gln Gln Ile Lys Ile Leu Lys His Val Pro Glu690 695 700 Gly Ala Glu Thr Glu Gln Gly Leu Lys Arg Glu Leu Gln Val LeuArg 705 710 715 720 Leu Ala Asn His Gln Leu Asp Lys Glu Lys Ala Glu LeuIle His Gln 725 730 735 Ile Glu Ala Asn Lys Asp Gln Ser Gly Ala Glu SerThr Ile Pro Asp 740 745 750 Ala Asp Gln Leu Lys Lys Lys Lys Lys 755 76036 637 PRT Homo sapiens 36 Met Phe Arg Gln Ala Met Arg Thr Pro Ile IleTrp Phe His Val Val 1 5 10 15 Pro Ala Ala Asn Lys Glu Gln Tyr Glu GlnLeu Ser Gln Ser Glu Lys 20 25 30 Asn Asn Tyr Tyr Ser Ser Arg Phe Ser ProAsp Ser Gln Tyr Ile Asp 35 40 45 Asn Arg Ser Val Asn Ser Ala Gly Leu HisThr Val Gln Arg Ala Pro 50 55 60 Arg Leu Asn His Pro Pro Glu Gln Ile AspSer His Ser Arg Leu Pro 65 70 75 80 His Ser Ala His Pro Ser Gly Lys ProPro Ser Ala Pro Ala Ser Ala 85 90 95 Pro Gln Asn Val Phe Ser Thr Thr ValSer Ser Gly Tyr Asn Thr Lys 100 105 110 Lys Ile Gly Lys Arg Leu Asn IleGln Leu Lys Lys Gly Thr Glu Gly 115 120 125 Leu Glu Phe Ser Ile Thr SerArg Asp Val Thr Ile Gly Gly Ser Ala 130 135 140 Pro Ile Tyr Val Lys AsnIle Leu Pro Arg Gly Ala Ala Ile Gln Asp 145 150 155 160 Gly Arg Leu LysAla Gly Asp Arg Leu Ile Glu Val Asn Gly Val Asp 165 170 175 Leu Val GlyLys Ser Gln Glu Glu Val Val Ser Leu Leu Arg Ser Thr 180 185 190 Lys MetGlu Gly Thr Val Ser Leu Leu Val Phe Arg Gln Glu Asp Ala 195 200 205 PheHis Pro Arg Glu Leu Asn Ala Glu Pro Ser Gln Met Gln Ile Pro 210 215 220Lys Glu Thr Lys Ala Glu Asp Glu Asp Ile Val Leu Thr Pro Asp Gly 225 230235 240 Thr Arg Glu Phe Leu Thr Phe Glu Val Pro Leu Asn Asp Ser Gly Ser245 250 255 Ala Gly Leu Gly Val Ser Val Lys Gly Asn Arg Ser Lys Glu AsnHis 260 265 270 Ala Asp Leu Gly Ile Phe Val Lys Ser Ile Ile Asn Gly GlyAla Ala 275 280 285 Ser Lys Asp Gly Arg Leu Arg Val Asn Asp Gln Leu IleAla Val Asn 290 295 300 Gly Glu Ser Leu Leu Gly Lys Thr Asn Gln Asp AlaMet Glu Thr Leu 305 310 315 320 Arg Arg Ser Met Ser Thr Glu Gly Asn LysArg Gly Met Ile Gln Leu 325 330 335 Ile Val Ala Arg Arg Ile Ser Lys CysAsn Glu Leu Lys Ser Pro Gly 340 345 350 Ser Pro Pro Gly Pro Glu Leu ProIle Glu Thr Ala Leu Asp Asp Arg 355 360 365 Glu Arg Arg Ile Ser His SerLeu Tyr Ser Gly Ile Glu Gly Leu Asp 370 375 380 Glu Ser Pro Ser Arg AsnAla Ala Leu Ser Arg Ile Met Gly Glu Ser 385 390 395 400 Gly Lys Tyr GlnLeu Ser Pro Thr Val Asn Met Pro Gln Asp Asp Thr 405 410 415 Val Ile IleGlu Asp Asp Arg Leu Pro Val Leu Pro Pro His Leu Ser 420 425 430 Asp GlnSer Ser Ser Ser Ser His Asp Asp Val Gly Phe Val Thr Ala 435 440 445 AspAla Gly Thr Trp Ala Lys Ala Ala Ile Ser Asp Ser Ala Asp Cys 450 455 460Ser Leu Ser Pro Asp Val Asp Pro Val Leu Ala Phe Gln Arg Glu Gly 465 470475 480 Phe Gly Arg Gln Ile Ala Asp Glu Thr Lys Leu Asn Thr Val Asp Asp485 490 495 Gln Lys Ala Gly Ser Pro Ser Arg Asp Val Gly Pro Ser Leu GlyLeu 500 505 510 Lys Lys Ser Ser Ser Leu Glu Ser Leu Gln Thr Ala Val AlaGlu Val 515 520 525 Thr Leu Asn Gly Asp Ile Pro Phe His Arg Pro Arg ProArg Ile Ile 530 535 540 Arg Gly Arg Gly Cys Asn Glu Ser Phe Arg Ala AlaIle Asp Lys Ser 545 550 555 560 Tyr Asp Lys Pro Ala Val Asp Asp Asp AspGlu Gly Met Glu Thr Leu 565 570 575 Glu Glu Asp Thr Glu Glu Ser Ser ArgSer Gly Arg Glu Ser Val Ser 580 585 590 Thr Ala Ser Asp Gln Pro Ser HisSer Leu Glu Arg Gln Met Asn Gly 595 600 605 Asn Gln Glu Lys Gly Asp LysThr Asp Arg Lys Lys Lys Lys Lys Lys 610 615 620 Lys Lys Lys Lys Lys LysLys Lys Lys Lys Lys Lys Lys 625 630 635 37 764 PRT Homo sapiens 37 MetLeu Leu Asp Pro Thr Asn Pro Ser Ala Gly Thr Ala Lys Ile Asp 1 5 10 15Lys Gln Glu Lys Val Lys Leu Asn Phe Asp Met Thr Ala Ser Pro Lys 20 25 30Ile Leu Met Ser Lys Pro Val Leu Ser Gly Gly Thr Gly Arg Arg Ile 35 40 45Ser Leu Ser Asp Met Pro Arg Ser Pro Met Ser Thr Asn Ser Ser Val 50 55 60His Thr Gly Ser Asp Val Glu Gln Asp Ala Glu Lys Lys Ala Thr Ser 65 70 7580 Ser His Phe Ser Ala Ser Glu Glu Ser Met Asp Phe Leu Asp Lys Ser 85 9095 Thr Ala Ser Pro Ala Ser Thr Lys Thr Gly Gln Ala Gly Ser Leu Ser 100105 110 Gly Ser Pro Lys Pro Phe Ser Pro Gln Leu Ser Ala Pro Ile Thr Thr115 120 125 Lys Thr Asp Lys Thr Ser Thr Thr Gly Ser Ile Leu Asn Leu AsnLeu 130 135 140 Asp Arg Ser Lys Ala Glu Met Asp Leu Lys Glu Leu Ser GluSer Val 145 150 155 160 Gln Gln Gln Ser Thr Pro Val Pro Leu Ile Ser ProLys Arg Gln Ile 165 170 175 Arg Ser Arg Phe Gln Leu Asn Leu Asp Lys ThrIle Glu Ser Cys Lys 180 185 190 Ala Gln Leu Gly Ile Asn Glu Ile Ser GluAsp Val Tyr Thr Ala Val 195 200 205 Glu His Ser Asp Ser Glu Asp Ser GluLys Ser Asp Ser Ser Asp Ser 210 215 220 Glu Tyr Ile Ser Asp Asp Glu GlnLys Ser Lys Asn Glu Pro Glu Asp 225 230 235 240 Thr Glu Asp Lys Glu GlyCys Gln Met Asp Lys Glu Pro Ser Ala Val 245 250 255 Lys Lys Lys Pro LysPro Thr Asn Pro Val Glu Ile Lys Glu Glu Leu 260 265 270 Lys Ser Thr SerPro Ala Ser Glu Lys Ala Asp Pro Gly Ala Val Lys 275 280 285 Asp Lys AlaSer Pro Glu Pro Glu Lys Asp Phe Ser Glu Lys Ala Lys 290 295 300 Pro SerPro His Pro Ile Lys Asp Lys Leu Lys Gly Lys Asp Glu Thr 305 310 315 320Asp Ser Pro Thr Val His Leu Gly Leu Asp Ser Asp Ser Glu Ser Glu 325 330335 Leu Val Ile Asp Leu Gly Glu Asp His Ser Gly Arg Glu Gly Arg Lys 340345 350 Asn Lys Lys Glu Pro Lys Glu Pro Ser Pro Lys Gln Asp Val Val Gly355 360 365 Lys Thr Pro Pro Ser Thr Thr Val Gly Ser His Ser Pro Pro GluThr 370 375 380 Pro Val Leu Thr Arg Ser Ser Ala Gln Thr Ser Ala Ala GlyAla Thr 385 390 395 400 Ala Thr Thr Ser Thr Ser Ser Thr Val Thr Val ThrAla Pro Ala Pro 405 410 415 Ala Ala Thr Gly Ser Pro Val Lys Lys Gln ArgPro Leu Leu Pro Lys 420 425 430 Glu Thr Ala Pro Ala Val Gln Arg Val ValTrp Asn Ser Ser Thr Val 435 440 445 Gln Gln Lys Glu Ile Thr Gln Ser ProSer Thr Ser Thr Ile Thr Leu 450 455 460 Val Thr Ser Thr Gln Ser Ser AlaLeu Val Thr Ser Ser Gly Ser Met 465 470 475 480 Ser Thr Leu Val Ser SerVal Asn Ala Asp Leu Pro Ile Ala Thr Ala 485 490 495 Ser Ala Asp Val AlaAla Asp Ile Ala Lys Tyr Thr Ser Lys Met Met 500 505 510 Asp Ala Ile LysGly Thr Met Thr Glu Ile Tyr Asn Asp Leu Ser Lys 515 520 525 Asn Thr ThrGly Ser Thr Ile Ala Glu Ile Arg Arg Leu Arg Ile Glu 530 535 540 Ile GluLys Leu Gln Trp Leu His Gln Gln Glu Leu Ser Glu Met Lys 545 550 555 560His Asn Leu Glu Leu Thr Met Ala Glu Met Arg Gln Ser Leu Glu Gln 565 570575 Glu Arg Asp Arg Leu Ile Ala Glu Val Lys Lys Gln Leu Glu Leu Glu 580585 590 Lys Gln Gln Ala Val Asp Glu Thr Lys Lys Lys Gln Trp Cys Ala Asn595 600 605 Cys Lys Lys Glu Ala Ile Phe Tyr Cys Cys Trp Asn Thr Ser TyrCys 610 615 620 Asp Tyr Pro Cys Gln Gln Ala His Trp Pro Glu His Met LysSer Cys 625 630 635 640 Thr Gln Ser Ala Thr Ala Pro Gln Gln Glu Ala AspAla Glu Val Asn 645 650 655 Thr Glu Thr Leu Asn Lys Ser Ser Gln Gly SerSer Ser Ser Thr Gln 660 665 670 Ser Ala Pro Ser Glu Thr Ala Ser Ala SerLys Glu Lys Glu Thr Ser 675 680 685 Ala Glu Lys Ser Lys Glu Ser Gly SerThr Leu Asp Leu Ser Gly Ser 690 695 700 Arg Glu Thr Pro Ser Ser Ile LeuLeu Gly Ser Asn Gln Gly Ser Asp 705 710 715 720 His Ser Arg Ser Asn LysSer Ser Trp Ser Ser Ser Asp Glu Lys Arg 725 730 735 Gly Ser Thr Arg SerAsp His Asn Thr Ser Thr Ser Thr Lys Ser Leu 740 745 750 Leu Pro Lys GluSer Arg Leu Asp Thr Phe Trp Asp 755 760 38 623 PRT Homo sapiens 38 MetAla Glu Lys Thr Lys Leu Ile Thr Gln Leu Arg Asp Ala Lys Asn 1 5 10 15Leu Ile Glu Gln Leu Glu Gln Asp Lys Gly Met Val Ile Ala Glu Thr 20 25 30Lys Arg Gln Met His Glu Thr Leu Glu Met Lys Glu Glu Glu Ile Ala 35 40 45Gln Leu Arg Ser Arg Ile Lys Gln Met Thr Thr Gln Gly Glu Glu Leu 50 55 60Arg Glu Gln Lys Glu Lys Ser Glu Arg Ala Ala Phe Glu Glu Leu Glu 65 70 7580 Lys Ala Leu Ser Thr Ala Gln Lys Thr Glu Glu Ala Arg Arg Lys Leu 85 9095 Lys Ala Glu Met Asp Glu Gln Ile Lys Thr Ile Glu Lys Thr Ser Glu 100105 110 Glu Glu Arg Ile Ser Leu Gln Gln Glu Leu Ser Arg Val Lys Gln Glu115 120 125 Val Val Asp Val Met Lys Lys Ser Ser Glu Glu Gln Ile Ala LysLeu 130 135 140 Gln Lys Leu His Glu Lys Glu Leu Ala Arg Lys Glu Gln GluLeu Thr 145 150 155 160 Lys Lys Leu Gln Thr Arg Glu Arg Glu Phe Gln GluGln Met Lys Val 165 170 175 Ala Leu Glu Lys Ser Gln Ser Glu Tyr Leu LysIle Ser Gln Glu Lys 180 185 190 Glu Gln Gln Glu Ser Leu Ala Leu Glu GluLeu Glu Leu Gln Lys Lys 195 200 205 Ala Ile Leu Thr Glu Ser Glu Asn LysLeu Arg Asp Leu Gln Gln Glu 210 215 220 Ala Glu Thr Tyr Arg Thr Arg IleLeu Glu Leu Glu Ser Ser Leu Glu 225 230 235 240 Lys Ser Leu Gln Glu AsnLys Asn Gln Ser Lys Asp Leu Ala Val His 245 250 255 Leu Glu Ala Glu LysAsn Lys His Asn Met Glu Ile Thr Val Met Val 260 265 270 Glu Lys His LysThr Glu Leu Glu Ser Leu Lys His Gln Gln Asp Ala 275 280 285 Leu Trp ThrGlu Lys Leu Gln Val Leu Lys Gln Gln Tyr Gln Thr Glu 290 295 300 Met GluLys Leu Arg Glu Lys Cys Glu Gln Glu Lys Glu Thr Leu Leu 305 310 315 320Lys Asp Lys Glu Ile Ile Phe Gln Ala His Ile Glu Glu Met Asn Glu 325 330335 Lys Thr Leu Glu Lys Leu Asp Val Lys Gln Thr Glu Leu Glu Ser Leu 340345 350 Ser Ser Glu Leu Ser Glu Val Leu Lys Ala Arg His Lys Leu Glu Glu355 360 365 Glu Leu Ser Val Leu Lys Asp Gln Thr Asp Lys Met Lys Gln GluLeu 370 375 380 Glu Ala Lys Met Asp Glu Gln Lys Asn His His Gln Gln GlnVal Asp 385 390 395 400 Ser Ile Ile Lys Glu His Glu Val Ser Ile Gln ArgThr Glu Lys Ala 405 410 415 Leu Lys Asp Gln Ile Asn Gln Leu Glu Leu LeuLeu Lys Glu Arg Asp 420 425 430 Lys His Leu Lys Glu His Gln Ala His ValGlu Asn Leu Glu Ala Asp 435 440 445 Ile Lys Arg Ser Glu Gly Glu Leu GlnGln Ala Ser Ala Lys Leu Asp 450 455 460 Val Phe Gln Ser Tyr Gln Ser AlaThr His Glu Gln Thr Lys Ala Tyr 465 470 475 480 Glu Glu Gln Leu Ala GlnLeu Gln Gln Lys Leu Leu Asp Leu Glu Thr 485 490 495 Glu Arg Ile Leu LeuThr Lys Gln Val Ala Glu Val Glu Ala Gln Lys 500 505 510 Lys Asp Val CysThr Glu Leu Asp Ala His Lys Ile Gln Val Gln Asp 515 520 525 Leu Met GlnGln Leu Glu Lys Gln Asn Ser Glu Met Glu Gln Lys Val 530 535 540 Lys SerLeu Thr Gln Val Tyr Glu Ser Lys Leu Glu Asp Gly Asn Lys 545 550 555 560Glu Gln Glu Gln Thr Lys Gln Ile Leu Val Glu Lys Glu Asn Met Ile 565 570575 Leu Gln Met Arg Glu Gly Gln Lys Lys Glu Ile Glu Ile Leu Thr Gln 580585 590 Lys Leu Ser Ala Lys Glu Asp Ser Ile His Ile Leu Asn Glu Glu Tyr595 600 605 Glu Thr Lys Phe Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys610 615 620 39 1235 PRT Homo sapiens 39 Met Ser Phe Phe Asn Phe Arg LysIle Phe Lys Leu Gly Ser Glu Lys 1 5 10 15 Lys Lys Lys Gln Tyr Glu HisVal Lys Arg Asp Leu Asn Pro Glu Asp 20 25 30 Phe Trp Glu Ile Ile Gly GluLeu Gly Asp Gly Ala Phe Gly Lys Val 35 40 45 Tyr Lys Ala Gln Asn Lys GluThr Ser Val Leu Ala Ala Ala Lys Val 50 55 60 Ile Asp Thr Lys Ser Glu GluGlu Leu Glu Asp Tyr Met Val Glu Ile 65 70 75 80 Asp Ile Leu Ala Ser CysAsp His Pro Asn Ile Val Lys Leu Leu Asp 85 90 95 Ala Phe Tyr Tyr Glu AsnAsn Leu Trp Ile Leu Ile Glu Phe Cys Ala 100 105 110 Gly Gly Ala Val AspAla Val Met Leu Glu Leu Glu Arg Pro Leu Thr 115 120 125 Glu Ser Gln IleGln Val Val Cys Lys Gln Thr Leu Asp Ala Leu Asn 130 135 140 Tyr Leu HisAsp Asn Lys Ile Ile His Arg Asp Leu Lys Ala Gly Asn 145 150 155 160 IleLeu Phe Thr Leu Asp Gly Asp Ile Lys Leu Ala Asp Phe Gly Val 165 170 175Ser Ala Lys Asn Thr Arg Thr Ile Gln Arg Arg Asp Ser Phe Ile Gly 180 185190 Thr Pro Tyr Trp Met Ala Pro Glu Val Val Met Cys Glu Thr Ser Lys 195200 205 Asp Arg Pro Tyr Asp Tyr Lys Ala Asp Val Trp Ser Leu Gly Ile Thr210 215 220 Leu Ile Glu Met Ala Glu Ile Glu Pro Pro His His Glu Leu AsnPro 225 230 235 240 Met Arg Val Leu Leu Lys Ile Ala Lys Ser Glu Pro ProThr Leu Ala 245 250 255 Gln Pro Ser Arg Trp Ser Ser Asn Phe Lys Asp PheLeu Lys Lys Cys 260 265 270 Leu Glu Lys Asn Val Asp Ala Arg Trp Thr ThrSer Gln Leu Leu Gln 275 280 285 His Pro Phe Val Thr Val Asp Ser Asn LysPro Ile Arg Glu Leu Ile 290 295 300 Ala Glu Ala Lys Ala Glu Val Thr GluGlu Val Glu Asp Gly Lys Glu 305 310 315 320 Glu Asp Glu Glu Glu Glu ThrGlu Asn Ser Leu Pro Ile Pro Ala Ser 325 330 335 Lys Arg Ala Ser Ser AspLeu Ser Ile Ala Ser Ser Glu Glu Asp Lys 340 345 350 Leu Ser Gln Asn AlaCys Ile Leu Glu Ser Val Ser Glu Lys Thr Glu 355 360 365 Arg Ser Asn SerGlu Asp Lys Leu Asn Ser Lys Ile Leu Asn Glu Lys 370 375 380 Pro Thr ThrAsp Glu Pro Glu Lys Ala Val Glu Asp Ile Asn Glu His 385 390 395 400 IleThr Asp Ala Gln Leu Glu Ala Met Thr Glu Leu His Asp Arg Thr 405 410 415Ala Val Ile Lys Glu Asn Glu Arg Glu Lys Arg Pro Lys Leu Glu Asn 420 425430 Leu Pro Asp Thr Glu Asp Gln Glu Thr Val Asp Ile Asn Ser Val Ser 435440 445 Glu Gly Lys Glu Asn Asn Ile Met Ile Thr Leu Glu Thr Asn Ile Glu450 455 460 His Asn Leu Lys Ser Glu Glu Glu Lys Asp Gln Glu Lys Gln GlnMet 465 470 475 480 Phe Glu Asn Lys Leu Ile Lys Ser Glu Glu Ile Lys AspThr Ile Leu 485 490 495 Gln Thr Val Asp Leu Val Ser Gln Glu Thr Gly GluLys Glu Ala Asn 500 505 510 Ile Gln Ala Val Asp Ser Glu Val Gly Leu ThrLys Glu Asp Thr Gln 515 520 525 Glu Lys Leu Gly Glu Asp Asp Lys Thr GlnLys Asp Val Ile Ser Asn 530 535 540 Thr Ser Asp Val Ile Gly Thr Cys GluAla Ala Asp Val Ala Gln Lys 545 550 555 560 Val Asp Glu Asp Ser Ala GluAsp Thr Gln Ser Asn Asp Gly Lys Glu 565 570 575 Val Val Glu Val Gly GlnLys Leu Ile Asn Lys Pro Met Val Gly Pro 580 585 590 Glu Ala Gly Gly ThrLys Glu Val Pro Ile Lys Glu Ile Val Glu Met 595 600 605 Asn Glu Ile GluGlu Gly Lys Asn Lys Glu Gln Ala Ile Asn Ser Ser 610 615 620 Glu Asn IleMet Asp Ile Asn Glu Glu Pro Gly Thr Thr Glu Gly Glu 625 630 635 640 GluIle Thr Glu Ser Ser Ser Thr Glu Glu Met Glu Val Arg Ser Val 645 650 655Val Ala Asp Thr Asp Gln Lys Ala Leu Gly Ser Glu Val Gln Asp Ala 660 665670 Ser Lys Val Thr Thr Gln Ile Asp Lys Glu Lys Lys Glu Ile Pro Val 675680 685 Ser Ile Lys Lys Glu Pro Glu Val Thr Val Val Ser Gln Pro Thr Glu690 695 700 Pro Gln Pro Val Leu Ile Pro Ser Ile Asn Ile Asn Ser Asp SerGly 705 710 715 720 Glu Asn Lys Glu Glu Ile Gly Ser Leu Ser Lys Thr GluThr Ile Leu 725 730 735 Pro Pro Glu Ser Glu Asn Pro Lys Glu Asn Asp AsnAsp Ser Gly Thr 740 745 750 Gly Ser Thr Ala Asp Thr Ser Ser Ile Asp LeuAsn Leu Ser Ile Ser 755 760 765 Ser Phe Leu Ser Lys Thr Lys Asp Ser GlySer Ile Ser Leu Gln Glu 770 775 780 Thr Arg Arg Gln Lys Lys Thr Leu LysLys Thr Arg Lys Phe Ile Val 785 790 795 800 Asp Gly Val Glu Val Ser ValThr Thr Ser Lys Ile Val Thr Asp Ser 805 810 815 Asp Ser Lys Thr Glu GluLeu Arg Phe Leu Arg Arg Gln Glu Leu Arg 820 825 830 Glu Leu Arg Phe LeuGln Lys Glu Glu Gln Arg Ala Gln Gln Gln Leu 835 840 845 Asn Ser Lys LeuGln Gln Gln Arg Glu Gln Ile Phe Arg Arg Phe Glu 850 855 860 Gln Glu MetMet Ser Lys Lys Arg Gln Tyr Asp Gln Glu Ile Glu Asn 865 870 875 880 LeuGlu Lys Gln Gln Lys Gln Thr Ile Glu Arg Leu Glu Gln Glu His 885 890 895Thr Asn Arg Leu Arg Asp Glu Ala Lys Arg Ile Lys Gly Glu Gln Glu 900 905910 Lys Glu Leu Ser Lys Phe Gln Asn Met Leu Lys Asn Arg Lys Lys Glu 915920 925 Val Ile Asn Glu Val Glu Lys Ala Pro Lys Glu Leu Arg Lys Glu Leu930 935 940 Met Lys Arg Arg Lys Glu Glu Leu Ala Gln Ser Gln His Ala GlnGlu 945 950 955 960 Gln Glu Phe Val Gln Lys Gln Gln Gln Glu Leu Asp GlySer Leu Lys 965 970 975 Lys Ile Ile Gln Gln Gln Lys Ala Glu Leu Ala AsnIle Glu Arg Glu 980 985 990 Cys Leu Asn Asn Lys Gln Gln Leu Met Arg AlaArg Glu Ala Ala Ile 995 1000 1005 Trp Glu Leu Glu Glu Arg His Leu GlnGlu Lys His Gln Leu Leu Lys 1010 1015 1020 Gln Gln Leu Lys Asp Gln TyrPhe Met Gln Arg His Gln Leu Leu Lys 1025 1030 1035 1040 Arg His Glu LysGlu Thr Glu Gln Met Gln Arg Tyr Asn Gln Arg Leu 1045 1050 1055 Ile GluGlu Leu Lys Asn Arg Gln Thr Gln Glu Arg Ala Arg Leu Pro 1060 1065 1070Lys Ile Gln Arg Ser Glu Ala Lys Thr Arg Met Ala Met Phe Lys Lys 10751080 1085 Ser Leu Arg Ile Asn Ser Thr Ala Thr Pro Asp Gln Asp Arg AspLys 1090 1095 1100 Ile Lys Gln Phe Ala Ala Gln Glu Glu Lys Arg Gln LysAsn Glu Arg 1105 1110 1115 1120 Met Ala Gln His Gln Lys His Glu Asn GlnMet Arg Asp Leu Gln Leu 1125 1130 1135 Gln Cys Glu Ala Asn Val Arg GluLeu His Gln Leu Gln Asn Glu Lys 1140 1145 1150 Cys His Leu Leu Val GluHis Glu Thr Gln Lys Leu Lys Glu Leu Asp 1155 1160 1165 Glu Glu His SerGln Glu Leu Lys Glu Trp Arg Glu Lys Leu Arg Pro 1170 1175 1180 Arg LysLys Thr Leu Glu Glu Glu Phe Ala Arg Lys Leu Gln Glu Gln 1185 1190 11951200 Glu Val Phe Phe Lys Met Thr Gly Glu Ser Glu Cys Leu Asn Pro Ser1205 1210 1215 Thr Gln Ser Arg Ile Ser Lys Phe Tyr Pro Ile Pro Ser LeuHis Ser 1220 1225 1230 Thr Gly Ser 1235 40 561 PRT Homo sapiens 40 MetLeu Ser Ser Ser Arg Asp Gln Arg Val Val Thr Ser Glu Asp Gln 1 5 10 15Val Gln Glu Gly Thr Lys Val Leu Lys Leu Lys Thr Lys Met Ala Asp 20 25 30Lys Glu Asn Met Lys Arg Pro Ala Glu Ser Lys Asn Asn Thr Val Val 35 40 45Gly Lys His Cys Ile Pro Leu Lys Pro Ser Asn Glu Leu Thr Asn Ser 50 55 60Thr Val Val Ile Asp Thr His Lys Pro Lys Asp Ser Asn Gln Thr Pro 65 70 7580 His Leu Leu Leu Thr Glu Asp Asp Pro Gln Ser Gln His Met Thr Leu 85 9095 Ser Gln Ala Phe His Leu Lys Asn Asn Ser Lys Lys Lys Gln Met Thr 100105 110 Thr Glu Lys Gln Lys Gln Asp Ala Asn Met Pro Lys Lys Pro Val Leu115 120 125 Gly Ser Tyr Arg Gly Gln Ile Val Gln Ser Lys Ile Asn Ser PheArg 130 135 140 Lys Pro Leu Gln Val Lys Asp Glu Ser Ser Ala Ala Thr LysLys Leu 145 150 155 160 Ser Ala Thr Ile Pro Lys Ala Thr Lys Pro Gln ProVal Asn Thr Ser 165 170 175 Ser Val Thr Val Lys Ser Asn Arg Ser Ser AsnLys Thr Ala Thr Thr 180 185 190 Lys Phe Val Ser Thr Thr Ser Gln Asn ThrGln Leu Val Arg Pro Pro 195 200 205 Ile Arg Ser His His Ser Asn Thr ArgAsp Thr Val Lys Gln Gly Ile 210 215 220 Ser Arg Thr Ser Ala Asn Val ThrIle Arg Lys Gly Pro His Glu Lys 225 230 235 240 Glu Leu Leu Gln Ser LysThr Ala Leu Ser Ser Val Lys Thr Ser Ser 245 250 255 Ser Gln Gly Ile IleArg Asn Lys Thr Leu Ser Arg Ser Ile Ala Ser 260 265 270 Glu Val Val AlaArg Pro Ala Ser Leu Ser Asn Asp Lys Leu Met Glu 275 280 285 Lys Ser GluPro Val Asp Gln Arg Arg His Thr Ala Gly Lys Ala Ile 290 295 300 Val AspSer Arg Ser Ala Gln Pro Lys Glu Thr Ser Glu Glu Arg Lys 305 310 315 320Ala Arg Leu Ser Glu Trp Lys Ala Gly Lys Gly Arg Val Leu Lys Arg 325 330335 Pro Pro Asn Ser Val Val Thr Gln His Glu Pro Ala Gly Gln Asn Glu 340345 350 Lys Pro Val Gly Ser Phe Trp Thr Thr Met Ala Glu Glu Asp Glu Gln355 360 365 Arg Leu Phe Thr Glu Lys Val Asn Asn Thr Phe Ser Glu Cys LeuAsn 370 375 380 Leu Ile Asn Glu Gly Cys Pro Lys Glu Asp Ile Leu Val ThrLeu Asn 385 390 395 400 Asp Leu Ile Lys Asn Ile Pro Asp Ala Lys Lys LeuVal Lys Tyr Trp 405 410 415 Ile Cys Leu Ala Leu Ile Glu Pro Ile Thr SerPro Ile Glu Asn Ile 420 425 430 Ile Ala Ile Tyr Glu Lys Ala Ile Leu AlaGly Ala Gln Pro Ile Glu 435 440 445 Glu Met Arg His Thr Ile Val Asp IleLeu Thr Met Lys Ser Gln Glu 450 455 460 Lys Ala Asn Leu Gly Glu Asn MetGlu Lys Ser Cys Ala Ser Lys Glu 465 470 475 480 Glu Val Lys Glu Val SerIle Glu Asp Thr Gly Val Asp Val Asp Pro 485 490 495 Glu Lys Leu Glu MetGlu Ser Lys Leu His Arg Asn Leu Leu Phe Gln 500 505 510 Asp Cys Glu LysGlu Gln Asp Asn Lys Thr Lys Asp Pro Thr His Asp 515 520 525 Val Lys ThrPro Asn Thr Glu Thr Arg Thr Ser Cys Leu Ile Lys Tyr 530 535 540 Asn ValSer Thr Thr Pro Tyr Leu Gln Ser Val Lys Lys Lys Gly Ala 545 550 555 560Val 41 214 PRT Homo sapiens 41 Met Thr Lys Thr Leu Pro Gly Gly Ile MetVal Asn Gly Ser Arg Leu 1 5 10 15 Lys Asn Leu Val Leu Thr Tyr Val AsnAla Ile Ser Ser Gly Asp Leu 20 25 30 Pro Cys Ile Glu Asn Ala Val Leu AlaLeu Ala Gln Arg Glu Asn Ser 35 40 45 Ala Ala Val Gln Lys Ala Ile Ala HisTyr Asp Gln Gln Met Gly Gln 50 55 60 Lys Val Gln Leu Pro Met Glu Thr LeuGln Glu Leu Leu Asp Leu His 65 70 75 80 Arg Thr Ser Glu Arg Glu Ala IleGlu Val Phe Met Lys Asn Ser Phe 85 90 95 Lys Asp Val Asp Gln Ser Phe GlnLys Glu Leu Glu Thr Leu Leu Asp 100 105 110 Ala Lys Gln Asn Asp Ile CysLys Arg Asn Leu Glu Ala Ser Ser Asp 115 120 125 Tyr Cys Ser Ala Leu LeuLys Asp Ile Phe Gly Pro Leu Glu Glu Ala 130 135 140 Val Lys Gln Gly IleTyr Ser Lys Pro Gly Gly His Asn Leu Phe Ile 145 150 155 160 Gln Lys ThrGlu Glu Leu Lys Ala Lys Tyr Tyr Arg Glu Pro Arg Lys 165 170 175 Gly IleGln Ala Glu Glu Val Leu Gln Lys Tyr Leu Lys Ser Lys Glu 180 185 190 SerVal Ser His Ala Ile Leu Gln Thr Asp Gln Ala Leu Thr Glu Thr 195 200 205Glu Lys Lys Lys Lys Lys 210 42 693 PRT Homo sapiens 42 Met Asp Arg ProAsp Glu Gly Pro Pro Ala Lys Thr Arg Arg Leu Ser 1 5 10 15 Ser Ser GluSer Pro Gln Arg Asp Pro Pro Pro Pro Pro Pro Pro Pro 20 25 30 Pro Leu LeuArg Leu Pro Leu Pro Pro Pro Gln Gln Arg Pro Arg Leu 35 40 45 Gln Glu GluThr Glu Ala Ala Gln Val Leu Ala Asp Met Arg Gly Val 50 55 60 Gly Leu GlyPro Ala Leu Pro Pro Pro Pro Pro Tyr Val Ile Leu Glu 65 70 75 80 Glu GlyGly Ile Arg Ala Tyr Phe Thr Leu Gly Ala Glu Cys Pro Gly 85 90 95 Trp AspSer Thr Ile Glu Ser Gly Tyr Gly Glu Ala Pro Pro Pro Thr 100 105 110 GluSer Leu Glu Ala Leu Pro Thr Pro Glu Ala Ser Gly Gly Ser Leu 115 120 125Glu Ile Asp Phe Gln Val Val Gln Ser Ser Ser Phe Gly Gly Glu Gly 130 135140 Ala Leu Glu Thr Cys Ser Ala Val Gly Trp Ala Pro Gln Arg Leu Val 145150 155 160 Asp Pro Lys Ser Lys Glu Glu Ala Ile Ile Ile Val Glu Asp GluAsp 165 170 175 Glu Asp Glu Arg Glu Ser Met Arg Ser Ser Arg Arg Arg ArgArg Arg 180 185 190 Arg Arg Arg Lys Gln Arg Lys Val Lys Arg Glu Ser ArgGlu Arg Asn 195 200 205 Ala Glu Arg Met Glu Ser Ile Leu Gln Ala Leu GluAsp Ile Gln Leu 210 215 220 Asp Leu Glu Ala Val Asn Ile Lys Ala Gly LysAla Phe Leu Arg Leu 225 230 235 240 Lys Arg Lys Phe Ile Gln Met Arg ArgPro Phe Leu Glu Arg Arg Asp 245 250 255 Leu Ile Ile Gln His Ile Pro GlyPhe Trp Val Lys Ala Phe Leu Asn 260 265 270 His Pro Arg Ile Ser Ile LeuIle Asn Arg Arg Asp Glu Asp Ile Phe 275 280 285 Arg Tyr Leu Thr Asn LeuGln Val Gln Asp Leu Arg His Ile Ser Met 290 295 300 Gly Tyr Lys Met LysLeu Tyr Phe Gln Thr Asn Pro Tyr Phe Thr Asn 305 310 315 320 Met Val IleVal Lys Glu Phe Gln Arg Asn Arg Ser Gly Arg Leu Val 325 330 335 Ser HisSer Thr Pro Ile Arg Trp His Arg Gly Gln Glu Pro Gln Ala 340 345 350 ArgArg His Gly Asn Gln Asp Ala Ser His Ser Phe Phe Ser Trp Phe 355 360 365Ser Asn His Ser Leu Pro Glu Ala Asp Arg Ile Ala Glu Ile Ile Lys 370 375380 Asn Asp Leu Trp Val Asn Pro Leu Arg Tyr Tyr Leu Arg Glu Arg Gly 385390 395 400 Ser Arg Ile Lys Arg Lys Lys Gln Glu Met Lys Lys Arg Lys ThrArg 405 410 415 Gly Arg Cys Glu Val Val Ile Met Glu Asp Ala Pro Asp TyrTyr Ala 420 425 430 Val Glu Asp Ile Phe Ser Glu Ile Ser Asp Ile Asp GluThr Ile His 435 440 445 Asp Ile Lys Ile Ser Asp Phe Met Glu Thr Thr AspTyr Phe Glu Thr 450 455 460 Thr Asp Asn Glu Ile Thr Asp Ile Asn Glu AsnIle Cys Asp Ser Glu 465 470 475 480 Asn Pro Asp His Asn Glu Val Pro AsnAsn Glu Thr Thr Asp Asn Asn 485 490 495 Glu Ser Ala Asp Asp His Glu ThrThr Asp Asn Asn Glu Ser Ala Asp 500 505 510 Asp Asn Asn Glu Asn Pro GluAsp Asn Asn Lys Asn Thr Asp Asp Asn 515 520 525 Glu Glu Asn Pro Asn AsnAsn Glu Asn Thr Tyr Gly Asn Asn Phe Phe 530 535 540 Lys Gly Gly Phe TrpGly Ser His Gly Asn Asn Gln Asp Ser Ser Asp 545 550 555 560 Ser Asp AsnGlu Ala Asp Glu Ala Ser Asp Asp Glu Asp Asn Asp Gly 565 570 575 Asn GluGly Asp Asn Glu Gly Ser Asp Asp Asp Gly Asn Glu Gly Asp 580 585 590 AsnGlu Gly Ser Asp Asp Asp Asp Arg Asp Ile Glu Tyr Tyr Glu Lys 595 600 605Val Ile Glu Asp Phe Asp Lys Asp Gln Ala Asp Tyr Glu Asp Val Ile 610 615620 Glu Ile Ile Ser Asp Glu Ser Val Glu Glu Glu Gly Ile Glu Glu Gly 625630 635 640 Ile Gln Gln Asp Glu Asp Ile Tyr Glu Glu Gly Asn Tyr Glu GluGlu 645 650 655 Gly Ser Glu Asp Val Trp Glu Glu Gly Glu Asp Ser Asp AspSer Asp 660 665 670 Leu Glu Asp Val Leu Gln Val Pro Asn Gly Trp Ala AsnPro Gly Lys 675 680 685 Arg Gly Lys Thr Gly 690 43 316 PRT Homo sapiens43 Met Ala Ser Arg Leu Leu Leu Asn Asn Gly Ala Lys Met Pro Ile Leu 1 510 15 Gly Leu Gly Thr Trp Lys Ser Pro Pro Gly Gln Val Thr Glu Ala Val 2025 30 Lys Val Ala Ile Asp Val Gly Tyr Arg His Ile Asp Cys Ala His Val 3540 45 Tyr Gln Asn Glu Asn Glu Val Gly Val Ala Ile Gln Glu Lys Leu Arg 5055 60 Glu Gln Val Val Lys Arg Glu Glu Leu Phe Ile Val Ser Lys Leu Trp 6570 75 80 Cys Thr Tyr His Glu Lys Gly Leu Val Lys Gly Ala Cys Gln Lys Thr85 90 95 Leu Ser Asp Leu Lys Leu Asp Tyr Leu Asp Leu Tyr Leu Ile His Trp100 105 110 Pro Thr Gly Phe Lys Pro Gly Lys Glu Phe Phe Pro Leu Asp GluSer 115 120 125 Gly Asn Val Val Pro Ser Asp Thr Asn Ile Leu Asp Thr TrpAla Ala 130 135 140 Met Glu Glu Leu Val Asp Glu Gly Leu Val Lys Ala IleGly Ile Ser 145 150 155 160 Asn Phe Asn His Leu Gln Val Glu Met Ile LeuAsn Lys Pro Gly Leu 165 170 175 Lys Tyr Lys Pro Ala Val Asn Gln Ile GluCys His Pro Tyr Leu Thr 180 185 190 Gln Glu Lys Leu Ile Gln Tyr Cys GlnSer Lys Gly Ile Val Val Thr 195 200 205 Ala Tyr Ser Pro Leu Gly Ser ProAsp Arg Pro Trp Ala Lys Pro Glu 210 215 220 Asp Pro Ser Leu Leu Glu AspPro Arg Ile Lys Ala Ile Ala Ala Lys 225 230 235 240 His Asn Lys Thr ThrAla Gln Val Leu Ile Arg Phe Pro Met Gln Arg 245 250 255 Asn Leu Val ValIle Pro Lys Ser Val Thr Pro Glu Arg Ile Ala Glu 260 265 270 Asn Phe LysVal Phe Asp Phe Glu Leu Ser Ser Gln Asp Met Thr Thr 275 280 285 Leu LeuSer Tyr Asn Arg Asn Trp Arg Val Cys Ala Leu Leu Ser Cys 290 295 300 ThrSer His Lys Asp Tyr Pro Phe His Glu Glu Phe 305 310 315 44 22 DNAArtificial Sequence Description of Artificial Sequence Primer 44gcaaaagcaa ttagacgcta cc 22 45 22 DNA Artificial Sequence Description ofArtificial Sequence Primer 45 cacagccctg ttcttcttta gc 22 46 27 DNAArtificial Sequence Description of Artificial Sequence Primer 46gtacagcaga aagcaagcaa ctgaatg 27 47 28 DNA Artificial SequenceDescription of Artificial Sequence Primer 47 ggaaattgga ttctaaagcagttccttc 28 48 22 DNA Artificial Sequence Description of ArtificialSequence Primer 48 ctatgaatcc aagaccaaag gc 22 49 22 DNA ArtificialSequence Description of Artificial Sequence Primer 49 ctccactttggtccttgtta gc 22 50 20 DNA Artificial Sequence Description of ArtificialSequence Primer 50 acccacgcag atttggaatc 20 51 19 DNA ArtificialSequence Description of Artificial Sequence Primer 51 aggctgatcactggctgtg 19 52 22 DNA Artificial Sequence Description of ArtificialSequence Primer 52 ccttattgta caatggggct tc 22 53 24 DNA ArtificialSequence Description of Artificial Sequence Primer 53 cagacacaaggaactgaagt aacg 24 54 22 DNA Artificial Sequence Description ofArtificial Sequence Primer 54 cactgccaag atagacaagc ag 22 55 22 DNAArtificial Sequence Description of Artificial Sequence Primer 55gctcttatcc aggaagtcca tg 22 56 26 DNA Artificial Sequence Description ofArtificial Sequence Primer 56 tacaggatct cagacatatc tccatg 26 57 26 DNAArtificial Sequence Description of Artificial Sequence Primer 57aaatgtcttc ccactgcata atagtc 26 58 26 DNA Artificial SequenceDescription of Artificial Sequence Primer 58 taaggaaaca attcagtcacataagg 26 59 26 DNA Artificial Sequence Description of ArtificialSequence Primer 59 ctgtagctta gcaatttgtt cttctg 26 60 25 DNA ArtificialSequence Description of Artificial Sequence Primer 60 ttatgaggcttagaatttca accac 25 61 25 DNA Artificial Sequence Description ofArtificial Sequence Primer 61 aaaggctttc aaaacatttt tcaac 25 62 27 DNAArtificial Sequence Description of Artificial Sequence Primer 62gtagagatca gagagttgtg acatctg 27 63 27 DNA Artificial SequenceDescription of Artificial Sequence Primer 63 tattactttt cactgttacactgctgg 27 64 24 DNA Artificial Sequence Description of ArtificialSequence Primer 64 gccacagaga atgaaccact taac 24 65 23 DNA ArtificialSequence Description of Artificial Sequence Primer 65 gagggactatcagttgctgt ttg 23 66 26 DNA Artificial Sequence Description ofArtificial Sequence Primer 66 gcatctaata gaacgctact accacc 26 67 25 DNAArtificial Sequence Description of Artificial Sequence Primer 67ctgtgagcta tcacctatcc ttgag 25 68 26 DNA Artificial Sequence Descriptionof Artificial Sequence Primer 68 gtgacagtga ccacagaaat tccccc 26 69 24DNA Artificial Sequence Description of Artificial Sequence Primer 69cacgtttctc agagctgctg ctcc 24 70 30 DNA Artificial Sequence Descriptionof Artificial Sequence Primer 70 gctgcacaga aaaccttact tgtttccacc 30 7128 DNA Artificial Sequence Description of Artificial Sequence Primer 71ctcgtaaatg cagaaatctc caatgccc 28 72 26 DNA Artificial SequenceDescription of Artificial Sequence Primer 72 tccacagcct attggctcacttggac 26 73 30 DNA Artificial Sequence Description of ArtificialSequence Primer 73 gccctttagt gtgtctgtaa ttggaatcag 30 74 24 DNAArtificial Sequence Description of Artificial Sequence Primer 74gcacacactg ctcctccacc tgac 24 75 27 DNA Artificial Sequence Descriptionof Artificial Sequence Primer 75 gctgctgctg tttacagaaa ggctcac 27 76 29DNA Artificial Sequence Description of Artificial Sequence Primer 76ggaaagttat ccacagctac tgaggaccc 29 77 29 DNA Artificial SequenceDescription of Artificial Sequence Primer 77 tcccctccat ttaatctccaaattcaccc 29 78 23 DNA Artificial Sequence Description of ArtificialSequence Primer 78 ctcagcattt gccgccgtaa ctt 23 79 24 DNA ArtificialSequence Description of Artificial Sequence Primer 79 gaaaactacaaatcccagga gcac 24 80 24 DNA Artificial Sequence Description ofArtificial Sequence Primer 80 ctcacgaaat atgagcttca ccac 24 81 27 DNAArtificial Sequence Description of Artificial Sequence Primer 81ttactgatcg tctgctccct agagtcc 27 82 27 DNA Artificial SequenceDescription of Artificial Sequence Primer 82 atcttctgct cagtcagaatcccatgc 27 83 23 DNA Artificial Sequence Description of ArtificialSequence Primer 83 tgttgtagat cacttcaagg tgc 23 84 26 DNA ArtificialSequence Description of Artificial Sequence Primer 84 ccatatccaaattcccttgg tgtgag 26 85 20 DNA Artificial Sequence Description ofArtificial Sequence Primer 85 tgagaatgag gtgggggtgg 20 86 19 DNAArtificial Sequence Description of Artificial Sequence Primer 86tggggaaccg gatcaggac 19 87 22 DNA Artificial Sequence Description ofArtificial Sequence Primer 87 gcatcctacc accaactcgt cc 22 88 23 DNAArtificial Sequence Description of Artificial Sequence Primer 88agttctgaga ccgttcttcc acc 23 89 23 DNA Artificial Sequence Descriptionof Artificial Sequence Primer 89 gctgcggaca taaatcttaa agc 23 90 20 DNAArtificial Sequence Description of Artificial Sequence Primer 90agggtctcac tctgattgcc 20 91 2428 DNA Homo sapiens 91 gcactgaggtcaccctccag gctgtggaac ctttgttctt tcactctttg caataaatct 60 tgctgctgctcactctttgg gtccacactg cctttatgag ctgtaacact cactgggaat 120 gtctgcagcttcactcctga agccagcgag accacgaacc caccaggagg aacaaacaac 180 tccagacgcgcagccttaag agctgtaaca ctcaccgcga aggtctgcag cttcactcct 240 gagccagccagaccacgaac ccaccagaag gaagaaactc caaacacatc cgaacatcag 300 aaggagcaaactcctgacac gccaccttta agaaccgtga cactcaacgc tagggtccgc 360 ggcttcattcttgaagtcag tgagaccaag aacccaccaa ttccggacac gctaattgtt 420 gtagatcatcacttcaaggt gcccatatct ttctagtgga aaaattattc tggcctccgc 480 tgcatacaaatcaggcaacc agaattctac atatataagg caaagtaaca tcctagacat 540 ggctttagagatccacatgt cagaccccat gtgcctcatc gagaacttta atgagcagct 600 gaaggttaatcaggaagctt tggagatcct gtctgccatt acgcaacctg tagttgtggt 660 agcgattgtgggcctctatc gcactggcaa atcctacctg atgaacaagc tggctgggaa 720 gaacaagggcttctctgttg catctacggt gcagtctcac accaagggaa tttggatatg 780 gtgtgtgcctcatcccaact ggccaaatca cacattagtt ctgcttgaca ccgagggcct 840 gggagatgtagagaaggctg acaacaagaa tgatatccag atctttgcac tggcactctt 900 actgagcagcacctttgtgt acaatactgt gaacaaaatt gatcagggtg ctatcgacct 960 actgcacaatgtgacagaac tgacagatct gctcaaggca agaaactcac ccgaccttga 1020 cagggttgaagatcctgctg actctgcgag cttcttccca gacttagtgt ggactctgag 1080 agatttctgcttaggcctgg aaatagatgg gcaacttgtc acaccagatg aatacctgga 1140 gaattccctaaggccaaagc aaggtagtga tcaaagagtt caaaatttca atttgccccg 1200 tctgtgtatacagaagttct ttccaaaaaa gaaatgcttt atctttgact tacctgctca 1260 ccaaaaaaagcttgcccaac ttgaaacact gcctgatgat gagctagagc ctgaatttgt 1320 gcaacaagtgacagaattct gttcctacat ctttagccat tctatgacca agactcttcc 1380 aggtggcatcatggtcaatg gatctcgtct aaagaacctg gtgctgacct atgtcaatgc 1440 catcagcagtggggatctgc cttgcataga gaatgcagtc ctggccttgg ctcagagaga 1500 gaactcagctgcagtgcaaa aggccattgc ccactatgac cagcaaatgg gccagaaagt 1560 gcagctgcccatggaaaccc tccaggagct gctggacctg cacaggacca gtgagaggga 1620 ggccattgaagtcttcatga aaaactcttt caaggatgta gaccaaagtt tccagaaaga 1680 attggagactctactagatg caaaacagaa tgacatttgt aaacggaacc tggaagcatc 1740 ctcggattattgctcggctt tacttaagga tatttttggt cctctagaag aagcagtgaa 1800 gcagggaatttattctaagc caggaggcca taatctcttc attcagaaaa cagaagaact 1860 gaaggcaaagtactatcggg agcctcggaa aggaatacag gctgaagaag ttctgcagaa 1920 atatttaaagtccaaggagt ctgtgagtca tgcaatatta cagactgacc aggctctcac 1980 agagacggaaaaaaagaaga aagaggcaca agtgaaagca gaagctgaaa aggctgaagc 2040 gcaaaggttggcggcgattc aaaggcagaa cgagcaaatg atgcaggaga gggagagact 2100 ccatcaggaacaagtgagac aaatggagat agccaaacaa aattggctgg cagagcaaca 2160 gaaaatgcaggaacaacaga tgcaggaaca ggctgcacag ctcagcacaa cattccaagc 2220 tcaaaatagaagccttctca gtgagctcca gcacgcccag aggactgtta ataacgatga 2280 tccatgtgttttactctaaa gtgctaaata tgggagtttc ctttttttac tctttgtcac 2340 tgatgacacaacagaaaaga aactgtagac cttgggacaa tcaacattta aataaacttt 2400 ataattattttttcaaactt tcaaaaaa 2428 92 586 PRT Homo sapiens 92 Met Ala Leu Glu IleHis Met Ser Asp Pro Met Cys Leu Ile Glu Asn 1 5 10 15 Phe Asn Glu GlnLeu Lys Val Asn Gln Glu Ala Leu Glu Ile Leu Ser 20 25 30 Ala Ile Thr GlnPro Val Val Val Val Ala Ile Val Gly Leu Tyr Arg 35 40 45 Thr Gly Lys SerTyr Leu Met Asn Lys Leu Ala Gly Lys Asn Lys Gly 50 55 60 Phe Ser Val AlaSer Thr Val Gln Ser His Thr Lys Gly Ile Trp Ile 65 70 75 80 Trp Cys ValPro His Pro Asn Trp Pro Asn His Thr Leu Val Leu Leu 85 90 95 Asp Thr GluGly Leu Gly Asp Val Glu Lys Ala Asp Asn Lys Asn Asp 100 105 110 Ile GlnIle Phe Ala Leu Ala Leu Leu Leu Ser Ser Thr Phe Val Tyr 115 120 125 AsnThr Val Asn Lys Ile Asp Gln Gly Ala Ile Asp Leu Leu His Asn 130 135 140Val Thr Glu Leu Thr Asp Leu Leu Lys Ala Arg Asn Ser Pro Asp Leu 145 150155 160 Asp Arg Val Glu Asp Pro Ala Asp Ser Ala Ser Phe Phe Pro Asp Leu165 170 175 Val Trp Thr Leu Arg Asp Phe Cys Leu Gly Leu Glu Ile Asp GlyGln 180 185 190 Leu Val Thr Pro Asp Glu Tyr Leu Glu Asn Ser Leu Arg ProLys Gln 195 200 205 Gly Ser Asp Gln Arg Val Gln Asn Phe Asn Leu Pro ArgLeu Cys Ile 210 215 220 Gln Lys Phe Phe Pro Lys Lys Lys Cys Phe Ile PheAsp Leu Pro Ala 225 230 235 240 His Gln Lys Lys Leu Ala Gln Leu Glu ThrLeu Pro Asp Asp Glu Leu 245 250 255 Glu Pro Glu Phe Val Gln Gln Val ThrGlu Phe Cys Ser Tyr Ile Phe 260 265 270 Ser His Ser Met Thr Lys Thr LeuPro Gly Gly Ile Met Val Asn Gly 275 280 285 Ser Arg Leu Lys Asn Leu ValLeu Thr Tyr Val Asn Ala Ile Ser Ser 290 295 300 Gly Asp Leu Pro Cys IleGlu Asn Ala Val Leu Ala Leu Ala Gln Arg 305 310 315 320 Glu Asn Ser AlaAla Val Gln Lys Ala Ile Ala His Tyr Asp Gln Gln 325 330 335 Met Gly GlnLys Val Gln Leu Pro Met Glu Thr Leu Gln Glu Leu Leu 340 345 350 Asp LeuHis Arg Thr Ser Glu Arg Glu Ala Ile Glu Val Phe Met Lys 355 360 365 AsnSer Phe Lys Asp Val Asp Gln Ser Phe Gln Lys Glu Leu Glu Thr 370 375 380Leu Leu Asp Ala Lys Gln Asn Asp Ile Cys Lys Arg Asn Leu Glu Ala 385 390395 400 Ser Ser Asp Tyr Cys Ser Ala Leu Leu Lys Asp Ile Phe Gly Pro Leu405 410 415 Glu Glu Ala Val Lys Gln Gly Ile Tyr Ser Lys Pro Gly Gly HisAsn 420 425 430 Leu Phe Ile Gln Lys Thr Glu Glu Leu Lys Ala Lys Tyr TyrArg Glu 435 440 445 Pro Arg Lys Gly Ile Gln Ala Glu Glu Val Leu Gln LysTyr Leu Lys 450 455 460 Ser Lys Glu Ser Val Ser His Ala Ile Leu Gln ThrAsp Gln Ala Leu 465 470 475 480 Thr Glu Thr Glu Lys Lys Lys Lys Glu AlaGln Val Lys Ala Glu Ala 485 490 495 Glu Lys Ala Glu Ala Gln Arg Leu AlaAla Ile Gln Arg Gln Asn Glu 500 505 510 Gln Met Met Gln Glu Arg Glu ArgLeu His Gln Glu Gln Val Arg Gln 515 520 525 Met Glu Ile Ala Lys Gln AsnTrp Leu Ala Glu Gln Gln Lys Met Gln 530 535 540 Glu Gln Gln Met Gln GluGln Ala Ala Gln Leu Ser Thr Thr Phe Gln 545 550 555 560 Ala Gln Asn ArgSer Leu Leu Ser Glu Leu Gln His Ala Gln Arg Thr 565 570 575 Val Asn AsnAsp Asp Pro Cys Val Leu Leu 580 585 93 26 DNA Artificial SequenceDescription of Artificial Sequence Primer 93 agaaggaaga aactccaaacacatcc 26

1. A diagnostic composition comprising at least one nucleic acidsequence whose modified expression is associated with a tumoral disease,wherein the nucleic acid sequence comprises Lg1-2 (FIG. 5) or GPB-TA(FIG. 23).
 2. A medicament comprising at least one nucleic acidsequence, whose modified expression is associated with a tumoraldisease, wherein the nucleic acid sequence comprises Lg1-2 (FIG. 5) orGBP-TA (FIG. 23).
 3. The diagnostic composition according to claim 1,wherein the nucleic acid sequence whose modified expression is connectedwith a tumoral disease, comprises a nucleic acid sequence: (a) which onaccount of the degeneration of the genetic code differs from a nucleicacid sequence defined in claim 1 as regards the codon sequence; (b)which hybridizes with a nucleic acid sequence of claim 1; or (c) whichis a fragment, an allelic variant or another variant of a nucleic acidsequence of claim
 1. 4. The nucleic acid sequence of claim 1 is a cDNAor a genomic DNA.
 5. A protein whose modified concentration is connectedwith a tumoral disease and is encoded by a nucleic acid sequence ofclaim
 1. 6. A diagnostic composition comprising at least one vector,wherein the vector comprising one of the nucleic acid sequencesaccording to claim 1, at least one protein encoded by a nucleic acidsequence according to claim 1, or at least one antibody directed againstthe protein.
 7. The diagnostic composition according to claim 6, whereinthe composition is used for the diagnosis or follow-up of a tumoraldisease.
 8. The diagnostic composition according to claim 7, wherein thecomposition is provided in the form of an ELISA, protein chip, nucleicacid chip or a membrane loaded with DNA, RNA or protein.
 9. A medicamentcomprising at least one vector, wherein the vector comprising one of thenucleic acid sequences according to claim 2, at least one proteinencoded by a nucleic acid sequence according to claim 2, or at least oneantibody directed against the protein.
 10. The medicament according toclaim 9, wherein the medicament is used for treating tumoral diseases.11. A method of using a nucleic acid sequence according to claim 1,wherein the nucleic acid is used for diagnosis or therapy of a tumoraldisease.
 12. A method of using a protein encoded by a nucleic acidsequence of claim 1, wherein the protein is used for diagnosis ortherapy of a tumoral disease.
 13. A method of using an antibody directedagainst a protein encoded by a nucleic acid sequence of claim 1, whereinthe antibody is used for diagnosis or therapy of a tumoral disease. 14.A method of using a protein encoded by a nucleic acid of claim 1 or anantibody directed against the protein, wherein the antibody or theprotein is used as a vaccination agent.
 15. The method of claim 12,wherein the protein is used for preparation of peptide-loadedantigen-presenting cells.
 16. The method of claim 12, wherein theprotein is used for preparation of tumor-specific T-cells.
 17. Thediagnostic composition according to claim 1, wherein the tumoral diseaseis cutaneous T-cell lymphomas.
 18. The medicament according to claim 2,wherein the tumoral disease is cutaneous T-cell lymphomas.
 19. Themethod according to claim 11, wherein the tumoral disease is cutaneousT-cell lymphomas.